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Taxonomy Information
- Species:
- Human immunodeficiency virus (Website 1):
- Common Name: Human immunodeficiency virus
- GenBank Taxonomy No.: 12721
- Description: AIDS is an extraordinary kind of a crisis. AIDS is unique in human history in its rapid spread, its extent and the depth of its impact. Since the first AIDS case was diagnosed in 1981, the world has struggled to come to grips with its extraordinary dimensions. Early efforts to mount an effective response were fragmented, piecemeal and vastly underresourced. Few communities recognized the dangers ahead, and even fewer were able to mount an effective response. Now, more than 20 years later, 20 million people are dead and 37.8 million people (range: 34.6 - 42.3 million) worldwide are living with HIV. And still, AIDS expands relentlessly, destroying peoples lives and in many cases seriously damaging the fabric of societies(UNAIDS et al., 2004). AIDS was first recognized in the United States in 1981, following an increase in the incidence of usually rare opportunistic infections (such as the pneumonia caused by Pneumocystis carinii) in homosexual men that were caused by a general immune deficiency. Human immunodeficiency virus (HIV) was first isolated in 1983 and by the mid-1980s it was evident that two types of HIV, with slightly different genome structures, were circulating in human populations. Both viruses are characterized by extensive genetic diversity; HIV-1 is phylogenetically divided into three groups - M, N and O, with the M group further split into 9 subtypes and 15 circulating recombinant forms. Today, group M has a near global distribution, whereas groups N and O are restricted to individuals of West African origin. HIV-2 is also most common in individuals from West Africa and is composed of seven subtypes. Despite its initial association with homosexual men, it is clear that HIV-1 and HIV-2 are now primarily transmitted by heterosexual intercourse and from mother to infant(Rambaut et al., 2004). Several independent isolates, called lymphadenopathy-associated virus or LAV, human T-cell lymphotropic virus type III, or HTLV-III, and AIDS-associated retrovirus or ARV by the laboratories of origin, are similar with respect to morphology, cytopathology, requirements for optimum reverse transcriptase activity, at least some antigenic properties, and some restriction endonuclease cleavage sites in viral DNA. Epidemiological studies show that infection by one of these viruses may be a necessary condition for the development of AIDS, although predisposing factors may contribute to the onset of the disease. Certain taxonomic issues need to be addressed with respect to the relationships among the human retroviruses at the nucleotide level. A probe representative of ARV-2 anneals under high stringency conditions to restriction enzyme DNA fragments from cells infected with LAV or with HTLV-III. Thus, these three retroviruses are closely related(Sanchez-Pescador et al., 1985).
- Variant(s):
- Human immunodeficiency virus type 1 (Website 2):
- Common Name: Human immunodeficiency virus type 1
- GenBank Taxonomy No.: 11676
- Parents: Human immunodeficiency virus
- Description: HIV-1 is most closely related to simian immunodeficiency virus chimpanzee (SIVcpz), which is found in some sub-species of chimpanzee (Pan troglodytes troglodytes and Pan troglodytes schweinfurthii) that inhabit parts of equatorial Western and Central Africa, respectively. SIVcpz from P. t. troglodytes is of most interest because it shares the closest relationship with the abundant HIV-1 M group. The geographical range of P. t. troglodytes also encompasses the region in Africa that has the greatest genetic diversity of HIV-1, containing groups M, N and O; such a distribution is expected if this was where HIV-1 first emerged(Rambaut et al., 2004).
- Human immunodeficiency virus type 2 (Website 3):
- Common Name: Human immunodeficiency virus type 2
- GenBank Taxonomy No.: 11709
- Parents: Human immunodeficiency virus
- Description: HIV-2 is most closely related to SIVsm5, which is found at high prevalence in sooty mangabey monkeys (Cercocebus atys). As with HIV-1, sooty mangabeys are most frequent in the regions of West Africa where HIV-2 is likely to have emerged(Rambaut et al., 2004).
- Human immunodeficiency virus type 3 (Website 4):
- Common Name: Human immunodeficiency virus type 3
- GenBank Taxonomy No.: 35274
- Parents: Human immunodeficiency virus
- Description: Described is a new variety of retrovirus designated HIV-3, also known as HIV-1 subtype O, samples of which are deposited in the European Collection of Animal Cell Cultures (ECACC) under V88060301(US Patent Office Website).
- Human immunodeficiency virus type 1 (ARV2/SF2 ISOLATE) (Website 5):
- Common Name: Human immunodeficiency virus type 1 (ARV2/SF2 ISOLATE)
- GenBank Taxonomy No.: 11685
- Parents: Human immunodeficiency virus
- Description: The complete DNA sequence of ARV-2 reveals a fundamental genetic structure similar to that of other retroviruses. A distinct group of human retroviruses has been isolated from patients with the acquired immune deficiency syndrome (AIDS) and individuals with related conditions, such as persistent lymphadenopathy. Several independent isolates, called lymphadenopathy-associated virus or LAV, human T-cell lymphotropic virus type III, or HTLV-III, and AIDS-associated retrovirus or ARV by the laboratories of origin, are similar with respect to morphology, cytopathology, requirements for optimum reverse transcriptase activity, at least some antigenic properties, and some restriction endonuclease cleavage sites in viral DNA. Epidemiological studies show that infection by one of these viruses may be a necessary condition for the development of AIDS, although predisposing factors may contribute to the onset of the disease. Certain taxonomic issues need to be addressed with respect to the relationships among the human retroviruses at the nucleotide level. A probe representative of ARV-2 anneals under high stringency conditions to restriction enzyme DNA fragments from cells infected with LAV or with HTLV-III. Thus, these three retroviruses are closely related(Sanchez-Pescador et al., 1985). Approximately 17% divergence was observed between HXB-3 and ARV-2 sequences, which was most pronounced in the extracellular region of the envelope protein. The observed differences in sequence probably reflect divergent evolution of strains separated in time and geography. ARV-2 was recently isolated from the west coast of the United States. The HTLV-III isolates for which nucleotide sequences have been determined were all obtained from the east coast about one year earlier. Regardless of the reasons, the fact that such divergence can occur, and that it is more pronounced in the extracellular portion of the envelope protein, is an important consideration in the design of both diagnostic reagents and possible vaccines(Crowl et al., 1985).
- Human immunodeficiency virus type 1 (BH10 ISOLATE) (Website 6):
- Common Name: Human immunodeficiency virus type 1 (BH10 ISOLATE)
- GenBank Taxonomy No.: 11678
- Parents: Human immunodeficiency virus
- Description: Clones BH10, BH8 and BH5 were derived from a library of SstI-digested DNA from HTLV-III-infected H9 cells cloned in lambda -gtWes_ lambda-B(Ratner et al., 1985).
- Human immunodeficiency virus type 1 (BH5 ISOLATE) (Website 7):
- Common Name: Human immunodeficiency virus type 1 (BH5 ISOLATE)
- GenBank Taxonomy No.: 11682
- Parents: Human immunodeficiency virus
- Description: Clones BH10, BH8 and BH5 were derived from a library of SstI-digested DNA from HTLV-III-infected H9 cells cloned in lambda -gtWes_ lambda-B(Ratner et al., 1985).
- Human immunodeficiency virus type 1 (BH7 ISOLATE) (Website 8):
- Human immunodeficiency virus type 1 (BH8 ISOLATE) (Website 9):
- Common Name: Human immunodeficiency virus type 1 (BH8 ISOLATE)
- GenBank Taxonomy No.: 11684
- Parents: Human immunodeficiency virus
- Description: Clones BH10, BH8 and BH5 were derived from a library of SstI-digested DNA from HTLV-III-infected H9 cells cloned in lambda-gtWes_ lambda-B(Ratner et al., 1985).
- Human immunodeficiency virus type 1 (BRAIN ISOLATE) (Website 10):
- Common Name: Human immunodeficiency virus type 1 (BRAIN ISOLATE)
- GenBank Taxonomy No.: 11693
- Parents: Human immunodeficiency virus
- Description: HIV-1 BR (BRAIN) was isolated from autopsied brain tissue (frozen unfixed for 2 years) by cocultivating minced brain tissue (from frontal, occipital, and parietal lobes) with 3-day-old phytohemagglutin (PHA)-stimulated peripheral blood lymphocytes (PBLs). When compared for the rate of replication HIV-1 BR was up to 10-fold lower than HIV-1 451. In the extent of cytopathicity to CD4+ cells, HIV-1 BR was also lower than HIV-1 451. In addition, HIV-1 BR replicated in ROHA and U937 cell lines but to lesser extent than the prototype virus HIV-1 LAV.
- Human immunodeficiency virus type 1 (BRU ISOLATE) (Website 11):
- Common Name: Human immunodeficiency virus type 1 (BRU ISOLATE)
- GenBank Taxonomy No.: 11686
- Parents: Human immunodeficiency virus
- Description: We designate our different AIDS virus isolates by three letters of patients names, lymphadenopathy-associated virus (LAV) BRU referring to the prototype AIDS virus isolated in 1983 from a French homosexual patient with lymphadenopathy syndrome (LAS), thought to have been previously infected in the USA(Alizon et al., 1986).
- Human immunodeficiency virus type 1 (CDC-451 ISOLATE) (Website 12):
- Common Name: Human immunodeficiency virus type 1 (CDC-451 ISOLATE)
- GenBank Taxonomy No.: 11687
- Parents: Human immunodeficiency virus
- Description: The lymphotropic retrovirus designated as HIV (CDC-451) was isolated from a 16-year-old white male with severe hemophilia A. Throughout his life, he had been treated with lyophilized factor VIII concentrates. He had no other known risk factors. Just before his death in June 1984, the virus was isolated from his peripheral blood by previously described methods. After two passages in phytohemagglutinin-stimulated normal adult human T cells, the virus was further propagated in Hut-78 cells obtained from the American Type Culture Collection(Desai et al., 1986).
- Human immunodeficiency virus type 1 (CLONE 12 ISOLATE) (Website 13):
- Human immunodeficiency virus type 1 (ELI ISOLATE) (Website 14):
- Common Name: Human immunodeficiency virus type 1 (ELI ISOLATE)
- GenBank Taxonomy No.: 11689
- Parents: Human immunodeficiency virus
- Description: Both of the African patients originated from Zaire; lymphadenopathy-associated virus (LAV) ELI was recovered in 1983 from a 24 year old woman with AIDS(Alizon et al., 1986).
- Human immunodeficiency virus type 1 (HXB2 ISOLATE) (Website 15):
- Common Name: Human immunodeficiency virus type 1 (HXB2 ISOLATE)
- GenBank Taxonomy No.: 11706
- Parents: Human immunodeficiency virus
- Description: Clone HXB2 was derived from a recombinant phage library of XbaI-digested DNA from HTLV-III-infected H9 cell cloned in lambda-J1(Ratner et al., 1985).
- Human immunodeficiency virus type 1 (HXB3 ISOLATE) (Website 16):
- Common Name: Human immunodeficiency virus type 1 (HXB3 ISOLATE)
- GenBank Taxonomy No.: 11707
- Parents: Human immunodeficiency virus
- Description: The integrated proviral genome of HTLV-III was recently cloned from the genomic DNA of H9 cells infected with HTLV-III. Since the HTLV-III provirus was found to lack Xba I restriction sites, a genomic library was constructed using Xba I digested H9/HTLV-III DNA. Screening of this library with HTLV-III cDNA probes yielded several clones, one of which, termed HXB-3 was used in the present study. Approximately 3% divergence was observed between the HTLV-III (HXB-3) and LAV amino acid sequences. However, among the three HTLV-III sequences (HXB-3, HB-10, BH-8), the divergence was 1.6%. Approximately 17% divergence was observed between HXB-3 and ARV-2 sequences, which was most pronounced in the extracellular region of the envelope protein. The observed differences in sequence probably reflect divergent evolution of strains separated in time and geography. ARV-2 was recently isolated from the west coast of the United States. The HTLV-III isolates for which nucleotide sequences have been determined were all obtained from the east coast about one year earlier. Regardless of the reasons, the fact that such divergence can occur, and that it is more pronounced in the extracellular portion of the envelope protein, is an important consideration in the design of both diagnostic reagents and possible vaccines(Crowl et al., 1985).
- Human immunodeficiency virus type 1 (JH3 ISOLATE) (Website 17):
- Common Name: Human immunodeficiency virus type 1 (JH3 ISOLATE)
- GenBank Taxonomy No.: 11694
- Parents: Human immunodeficiency virus
- Description: A strain of HIV-1 JH3 was isolated from a Japanese male 10 years old with hemophilia who was a carrier of HIV at the time of virus isolation (August 1986). Peripheral lymphocytes were cocultured with a human T cell line CEM under the standard conditions, and the virus replicated in CEM cells was termed JH3(Komiyama et al., 1989).
- Human immunodeficiency virus type 1 (JRCSF ISOLATE) (Website 18):
- Common Name: Human immunodeficiency virus type 1 (JRCSF ISOLATE)
- GenBank Taxonomy No.: 11688
- Parents: Human immunodeficiency virus
- Description: Patient J.R. died with Kaposis sarcoma and severe AIDS encephalopathy. The brain showed extensive leukoencephalopathy, and characteristic multinucleated giant cell syncytia were observed in pathologic specimens of frontal lobe brain tissue taken at autopsy. Virus was isolated from various tissue sources by infection of lectin-activated normal human peripheral blood lymphocytes (PBL). Two genotypically distinct viruses were obtained from the CNS of patient J.R. We will term these viruses HIV (JR-CSF) and HIV (JR-FL) for isolates derived from the cerebrospinal fluid and frontal lobe, respectively(Koyanagi et al., 1987).
- Human immunodeficiency virus type 1 (KB-1 ISOLATE) (Website 19):
- Common Name: Human immunodeficiency virus type 1 (KB-1 ISOLATE)
- GenBank Taxonomy No.: 36375
- Parents: Human immunodeficiency virus
- Description: HIV-1 strain KB-1gp41 was isolated from a Japanese male-hemophiliac by coculture of his peripheral blood mononuclear cells (PBMCs) with MT-2 cells(Shimizu et al., 1992).
- Human immunodeficiency virus type 1 (Lai ISOLATE) (Website 20):
- Human immunodeficiency virus type 1 (MAL ISOLATE) (Website 21):
- Common Name: Human immunodeficiency virus type 1 (MAL ISOLATE)
- GenBank Taxonomy No.: 11697
- Parents: Human immunodeficiency virus
- Description: Both of the African patients originated from Zaire; lymphadenopathy-associated virus (LAV) MAL in 1985 from a 7 year old boy with AIDS-related complex (ARC), probably infected in 1981 after a blood transfusion in Zaire, since his parents were LAV-seronegative(Alizon et al., 1986).
- Human immunodeficiency virus type 1 (MFA ISOLATE) (Website 22):
- Common Name: Human immunodeficiency virus type 1 (MFA ISOLATE)
- GenBank Taxonomy No.: 11704
- Parents: Human immunodeficiency virus
- Description: The primary virus isolate was obtained by cocultivation of peripheral blood lymphocytes from an HIV-1-seropositive asymptomatic hemophiliac with cells of the CD4+ cell line CEM(Stevenson et al., 1990).
- Human immunodeficiency virus type 1 (MN ISOLATE) (Website 23):
- Common Name: Human immunodeficiency virus type 1 (MN ISOLATE)
- GenBank Taxonomy No.: 11696
- Parents: Human immunodeficiency virus
- Description: The HIV-1 isolates HTLV-III(MN) and (SC) were obtained from a pediatric AIDS patient in the New York area in 1984 and a homosexual ARC (AIDS-related complex) patient from California in 1984, respectively. In the more constant regions of the env gene, HTLV-III(MN) and (SC), differ mostly by scattered point mutations, many of them resulting in conservative amino acid substitutions. A comparison of the inferred amino acid sequences of the env genes of other HIV-1 isolates for which DNA sequence data are available indicates that HTLV-III(MN) and (SC) differ over the entire length of their env genes from other US isolates to the same extent that they differ from HTLV-III (BH10) and to a significantly greater extent from several African isolates. They thus represent two new env genotypes of HIV-1(Gurgo et al., 1988).
- Human immunodeficiency virus type 1 (NDK ISOLATE) (Website 24):
- Common Name: Human immunodeficiency virus type 1 (NDK ISOLATE)
- GenBank Taxonomy No.: 11695
- Parents: Human immunodeficiency virus
- Description: A highly cytopathic strain of HIV1, named HIV1-NDK, has been isolated from a Zairian patient affected with AIDS. This isolate is 10(4) times more cytopathic and infectious than the prototype. To correlate the high cytopathic properties of this strain with genetic variations, we have cloned and sequenced the genome of this isolate. The principal feature which could be drawn from the fine analysis of the HIV1-NDK sequence is that the variability is not clustered in one particular region but rather spread out all along the genome. Only minor differences seem to be responsible for the acute biological effect of HIV1-NDK(Spire et al., 1989).
- Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE) (Website 25):
- Common Name: Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)
- GenBank Taxonomy No.: 11698
- Parents: Human immunodeficiency virus
- Description: Peripheral blood lymphocytes (PBL) were obtained from five New York City patients in October 1984, from three Zairian patients in October 1983, and from a patient living in Birmingham, Alabama in January 1985. The New York 5 isolate was from a man with AIDS(Benn et al., 1985).
- Human immunodeficiency virus type 1 (NIT-A ISOLATE) (Website 26):
- Common Name: Human immunodeficiency virus type 1 (NIT-A ISOLATE)
- GenBank Taxonomy No.: 36376
- Parents: Human immunodeficiency virus
- Description: We have previously described the isolation and molecular cloning of a family of HIV-1 isolates (HIV-1/N1T) from an individual with lymphadenopathy. Among these viruses, N1T-A behaves like prototypical HIV-1 isolates; its infection is rapid and cytopathic. N1T-E displays slow kinetics of infection and is not cytopathic, but like N1T-A, it is capable of efficient fusion and entry into target cells, expresses a transcriptionally active long terminal repeat (LTR) element, has functional tat and rev genes, and is highly productive in chronic infection in T lymphocytes and monocytes. Like other multiple isolates from one individual, N1T-E and N1T-A have similar restriction endonuclease maps and thus are closely related(Sakai et al., 1991).
- Human immunodeficiency virus type 1 (OYI ISOLATE) (Website 27):
- Common Name: Human immunodeficiency virus type 1 (OYI ISOLATE)
- GenBank Taxonomy No.: 11699
- Parents: Human immunodeficiency virus
- Description: An unusual HIV-1 strain has been isolated from the blood of a healthy Gabonese individual who presented an atypical western blot (WB). This virus, identified as isolated HIV-1OYl, grew to low titres of reverse transcriptase activity (less than 50,000 cpm/ml) and was not obviously cytopathic. Radioimmunoprecipitation and peptide ELISA studies indicated that the lack of env-specific reactivity was probably due to the absence of antibodies to the viral glycoproteins, rather than the virus encoding a highly divergent envelope protein(Huet et al., 1989).
- Human immunodeficiency virus type 1 (PV22 ISOLATE) (Website 28):
- Human immunodeficiency virus type 1 (RF/HAT ISOLATE) (Website 29):
- Common Name: Human immunodeficiency virus type 1 (RF/HAT ISOLATE)
- GenBank Taxonomy No.: 11701
- Parents: Human immunodeficiency virus
- Description: A strain of HTLV-III was isolated from fresh mononuclear cells from the peripheral blood of a Haitian patient, R. F., who was diagnosed with AIDS acquired through heterosexual transmission(Popovic et al., 1984).
- Human immunodeficiency virus type 1 (SC ISOLATE) (Website 30):
- Common Name: Human immunodeficiency virus type 1 (SC ISOLATE)
- GenBank Taxonomy No.: 11702
- Parents: Human immunodeficiency virus
- Description: The HIV-1 isolates HTLV-III(MN) and (SC) were obtained from a pediatric AIDS patient in the New York area in 1984 and a homosexual ARC (AIDS-related complex) patient from California in 1984, respectively. In the more constant regions of the env gene, HTLV-III(MN) and (SC), differ mostly by scattered point mutations, many of them resulting in conservative amino acid substitutions. A comparison of the inferred amino acid sequences of the env genes of other HIV-1 isolates for which DNA sequence data are available indicates that HTLV-III(MN) and (SC) differ over the entire length of their env genes from other US isolates to the same extent that they differ from HTLV-III (BH10) and to a significantly greater extent from several African isolates. They thus represent two new env genotypes of HIV-1(Gurgo et al., 1988).
- Human immunodeficiency virus type 1 (SF162 ISOLATE) (Website 31):
- Common Name: Human immunodeficiency virus type 1 (SF162 ISOLATE)
- GenBank Taxonomy No.: 11691
- Parents: Human immunodeficiency virus
- Description: HIV-1 SF162 was obtained by cocultivation of peripheral blood mononuclear cells (PMC) from seronegative donors with cerebrospinal cord fluid of a HIV-1-seropositive patient with toxoplasmosis(Cheng-Mayer et al., 1990).
- Human immunodeficiency virus type 1 (SF33 ISOLATE) (Website 32):
- Common Name: Human immunodeficiency virus type 1 (SF33 ISOLATE)
- GenBank Taxonomy No.: 11690
- Parents: Human immunodeficiency virus
- Description: HIV-l SF33 was obtained from the PMC of a patient with thrombocytopenia. The HIV-1 SF33 strain replicates rapidly and to high titers in the HUT 78 and CEM cell lines and productively infects HOS cells. This isolate is also very cytopathic and forms plaques in the MT-4 cell line. The molecular clones of HIV-l SF2 and HIV-l SF33 were found to be biologically active upon transfection into human rhabdomyosarcoma (RD-4) and HUT 78 cells. The biologic properties of the molecular clones showed characteristics identical to those of the parental viruses(York-Higgins et al., 1990).
- Human immunodeficiency virus type 1 (STRAIN UGANDAN / ISOLATE U455) (Website 33):
- Common Name: Human immunodeficiency virus type 1 (STRAIN UGANDAN / ISOLATE U455)
- GenBank Taxonomy No.: 11703
- Parents: Human immunodeficiency virus
- Description: U455 virus was isolated in December 1985 from peripheral blood lymphocytes (PBL) of a 35-year-old Ugandan male diagnosed to have slim disease and tuberculosis. We have made a large number of isolations of HIV-1 from seropositive asymptomatic individuals and from patients with slim disease, chiefly from the Kampala region of Uganda. We now describe the isolation and properties of a Ugandan virus(Oram et al., 1990).
- Human immunodeficiency virus type 1 (WMJ1 ISOLATE) (Website 34):
- Common Name: Human immunodeficiency virus type 1 (WMJ1 ISOLATE)
- GenBank Taxonomy No.: 31678
- Parents: Human immunodeficiency virus
- Description: Isolate WMJ-1 was similarly transmitted from the peripheral blood mononuclear cells of a Haitian infant with AIDS to an immortalized T cell line(Starcich et al., 1986).
- Human immunodeficiency virus type 1 (WMJ2 ISOLATE) (Website 35):
- Human immunodeficiency virus type 1 (YU-2 ISOLATE) (Website 36):
- Common Name: Human immunodeficiency virus type 1 (YU-2 ISOLATE)
- GenBank Taxonomy No.: 36377
- Parents: Human immunodeficiency virus
- Description: The viral clones HIV-1YU-2, HIV-l Yu-1 , HIV-1YU 21, and HIV-1YU-32 analyzed in this study were obtained as described previously directly from uncultured brain tissue of a man who died in 1986 at the age of 40 with severe (stage 3) ADC. Although the date of initial HIV-1 infection of this individual was unknown, he first presented with an AIDS-defining illness (Kaposi's sarcoma) in 1983 and then developed extraoral candidiasis, cytomegalovirus retinitis, and Pneumocystis carnii pneumonia in 1985. He never received AZT or other antiretroviral therapy. Immunohistological examination of the brain described previously revealed severe multinucleated giant cell encephalitis and widespread HIV-1 infection of macrophages and microglia. Because the HIV-1 clones were derived from this tissue by recombinant lambda phage cloning of permuted circular viral DNA intermediate forms, the viral inserts were excised by using unique restriction endonucleases (SailI, SphIT, and EcoRI) and reconstructed in the plasmid vector pTZ so as to yield full-length nonpermuted viral genomes(Li et al., 2002).
- Human immunodeficiency virus type 1 (Z-84 ISOLATE) (Website 37):
- Common Name: Human immunodeficiency virus type 1 (Z-84 ISOLATE)
- GenBank Taxonomy No.: 11681
- Parents: Human immunodeficiency virus
- Description: Peripheral mononuclear cells were isolated from a Zairian male with the acquired immunodeficiency syndrome (AIDS), age 52, phytohemagglutinin (PHA)-stimulated, and cocultivated with PHA-stimulated normal donor perhipheral mononuclear cells under standard conditions. H9 cells were infected with cell-free supernatant from the mononuclear cell cultures. This isolate of HIV-1, termed Z84, has been maintained in H9 cells(Yourno et al., 1988).
- Human immunodeficiency virus type 1 (Z2/CDC-Z34 ISOLATE) (Website 38):
- Human immunodeficiency virus type 1 (ZAIRE 3 ISOLATE) (Website 39):
- Human immunodeficiency virus type 1 (ZAIRE 6 ISOLATE) (Website 40):
- Common Name: Human immunodeficiency virus type 1 (ZAIRE 6 ISOLATE)
- GenBank Taxonomy No.: 11708
- Parents: Human immunodeficiency virus
- Description: We molecularly cloned the genome of HIV isolated from a Zairian AIDS patient. Restriction mapping of the recombinant clone, designated HIV-Zr6, revealed both common (as observed in other HIV isolates) and unique restriction sites. The DNA clone of HIV-Zr6, shown to give rise to infectious cytopathic virus after transfection of cultured lymphoid cells, was sequenced in several regions. The long terminal repeat (LTR), open reading frame 1 (ORF1), C-terminal envelope (env) gene domain, and ORF2 showed less than 6% difference in nucleotide sequence when compared to other HIV isolates including human T-lymphotropic virus-type III (HTLV-III) clone B10, lymphadenopathy-associated virus-1 (LAV-1), and AIDS-associated retrovirus-2 (ARV-2)(Srinivasan et al., 1987).
- Human immunodeficiency virus type 1 (ZAIRE HZ321 ISOLATE) (Website 41):
- Common Name: Human immunodeficiency virus type 1 (ZAIRE HZ321 ISOLATE)
- GenBank Taxonomy No.: 11692
- Parents: Human immunodeficiency virus
- Description: Human immunodeficiency virus type 1 (Z321 designate, HIV-1Z321), the oldest known HIV, was isolated from a serum sample collected in Zaire in 1976 and was molecularly cloned(Srinivasan et al., 1989).
- Human immunodeficiency virus type 1 (lw12.3 ISOLATE) (Website 42):
- Common Name: Human immunodeficiency virus type 1 (lw12.3 ISOLATE)
- GenBank Taxonomy No.: 82834
- Parents: Human immunodeficiency virus
- Description: Accidental infection of a laboratory worker (LW) with HIV-1 has been previously reported. LW was involved in high-volume production of concentrated HIV-1 (human T cell leukemia/lymphotropic virus [HTLV]-III). Although no obvious exposure incident could be documented and no symptoms of an acute HIV-1 seroconversion syndrome were apparent, seropositivity was noted during routine screening, and virus was subsequently isolated. HIV-1 isolates were established and grown at various times from September 1985 to February 1990 in three independent laboratories from the peripheral blood mononuclear cells (PBMCs) of LW(Reitz et al., 1994).
- Human immunodeficiency virus type 2 (BEN ISOLATE) (Website 43):
- Common Name: Human immunodeficiency virus type 2 (BEN ISOLATE)
- GenBank Taxonomy No.: 11714
- Parents: Human immunodeficiency virus
- Description: A HIV-2 strain named HIV-2ben was isolated from peripheral blood lymphocytes of a patient who, since 1984, had developed neurological symptoms such as Raynaud's syndrome, followed by paresthesia of extremities and ataxia, and finally paraparesis of the legs and incontinence. This new isolate could be distinguished from HIV-2rod by antibody-binding epitopes, peptide maps of core p24 and p18 polypeptides and restriction endonuclease cleavage pattern(Schneider et al., 1990).
- Human immunodeficiency virus type 2 (CAM2 ISOLATE) (Website 44):
- Common Name: Human immunodeficiency virus type 2 (CAM2 ISOLATE)
- GenBank Taxonomy No.: 11715
- Parents: Human immunodeficiency virus
- Description: We report the complete nucleotide sequence of a human immunodeficiency virus type 2 (HIV-2) isolate from Guinea-Bissau (HIV-2CAM2). The genomic organization of HIV-2CAM2 is identical to that of other HIV-2 isolates but contains a stop codon in the pol gene. The deduced amino acid sequences of the viral proteins show variation of 20% in the gag, pol and vpx regions, and 25 to 45% in the tat, env and nef regions when compared to other isolates of HIV-2. This is greater than the variation observed between isolates of HIV-1(Tristem et al., 1991).
- Human immunodeficiency virus type 2 (D194 ISOLATE) (Website 45):
- Common Name: Human immunodeficiency virus type 2 (D194 ISOLATE)
- GenBank Taxonomy No.: 11713
- Parents: Human immunodeficiency virus
- Description: HIV-2 D194 was isolated in 1987 from the peripheral blood of a Gambian male who lived in Germany since May 1986. The patient suffered from severe neurological symptoms (Neuro-AIDS) and died at the end of May 1987. The virus isolate is characterized by its excellent growth in cultivated primary human macrophages(Kuhnel et al., 1990).
- Human immunodeficiency virus type 2 (D205,7 ISOLATE) (Website 46):
- Common Name: Human immunodeficiency virus type 2 (D205,7 ISOLATE)
- GenBank Taxonomy No.: 11716
- Parents: Human immunodeficiency virus
- Description: We have previously reported the molecular cloning of HIV-2 D205. This isolate from a healthy woman from Ghana was biologically characterized by its good growth on macrophages and by the absence of cytopathic effects on lymphocytes. It was originally classified as HIV-2 by western blot analysis. We have now determined the complete nucleotide sequence of the clone HIV-2 D205.7, which encompasses 7,817 base pairs (bp) of the proviral genome starting form the left lont terminal repeat (LTR)(Dietrich et al., 1998).
- Human immunodeficiency virus type 2 (GHANA-1 ISOLATE) (Website 47):
- Common Name: Human immunodeficiency virus type 2 (GHANA-1 ISOLATE)
- GenBank Taxonomy No.: 11717
- Parents: Human immunodeficiency virus
- Description: We isolated a retrovirus that hybridized with an HIV-2 ROD probe from an AIDS patient in Ghana and named it HIV-2[GH-1]. The restriction endonuclease patterns of the HIV-2[GH-1] were quite different from those of HIV-2[ROD](Hasegawa et al., 1989).
- Human immunodeficiency virus type 2 (KR ISOLATE) (Website 48a):
- Human immunodeficiency virus type 2 (NIH-Z ISOLATE) (Website 48b):
- Human immunodeficiency virus type 2 (ROD ISOLATE) (Website 49):
- Common Name: Human immunodeficiency virus type 2 (ROD ISOLATE)
- GenBank Taxonomy No.: 11720
- Parents: Human immunodeficiency virus
- Description: The ROD isolate of HIV-2 was obtained in 1985 from an AIDS patient from Cape Verde Islands (offshore Senegal)(Guyader et al., 1987).
- Human immunodeficiency virus type 2 (SBL/ISY ISOLATE) (Website 50):
- Common Name: Human immunodeficiency virus type 2 (SBL/ISY ISOLATE)
- GenBank Taxonomy No.: 11718
- Parents: Human immunodeficiency virus
- Description: The comparison of the predicted amino acid sequence of the viral proteins of HIV-2 SBL/ISY revealed a divergence comparable to the divergence observed among HIV-1 Zairian isolates, which is higher than the divergence described among American isolates. The patients from whom the HIV-2 isolates were obtained originated from geographically neighboring African countries of Guinea Bissau (HIV-2 NIH-z), Cape Verde Islands (HIV-2 ROD), and Gambia (HIV- 2 SBL/ISY). The considerable degree of divergence among these HIV-2 isolates would suggest that HIV-2 has been present in the African population for a time similar to HIV-1(Franchini et al., 1989). In fact, the infectivity of HIV-2 SBL/ISY is not restricted to human cells, but we have shown in a parallel study that this virus infects and kills fresh peripheral blood T cells from rhesus macaques in vitro and infects the same animals in vivo(Franchini et al., 1989).
- Human immunodeficiency virus type 2 (ST ISOLATE) (Website 51):
- Common Name: Human immunodeficiency virus type 2 (ST ISOLATE)
- GenBank Taxonomy No.: 11721
- Parents: Human immunodeficiency virus
- Description: To elucidate determinants of HIV pathogenicity, we have begun to molecularly dissect a previously reported, nonfusogenic and noncytopathic HIV-2 isolate, termed HIV-2/ST, that was obtained from a healthy Senegalese prostitute. Although this virus replicated to high titers in tissue culture, it infected cells at a slower rate than did cytopathic strains of HIV-1 and HIV-2 and caused little or no cell killing and fusion. This was the case despite the fact that its external envelope glycoprotein was cleaved correctly, transported to the cell surface, and shown to bind to a specific epitope on CD4, which was recognized by OKT4a but not OKT4 antibodies. HIV-2/ST therefore appeared to bind to the CD4 molecule analogous to other HIVs, but it failed to fuse with CD4-bearing target cells, suggesting that its infectivity was greatly retarded at the level of cell entry(Kumar et al., 1990).
- Human immunodeficiency virus type 2 (ST/24.1C#2 ISOLATE) (Website 52):
- Common Name: Human immunodeficiency virus type 2 (ST/24.1C#2 ISOLATE)
- GenBank Taxonomy No.: 31681
- Parents: Human immunodeficiency virus
- Description: The present study was undertaken to investigate the glycoprotein regions responsible for differential syncytium formation by two genetically highly related but biologically distinct HIV-2 viruses. Recombinant vaccinia virus expresson of the env gene of HIV-2/ST (ST) (a previously described replication-competent but noncytopathic virus) indicated that the glycoprotein was deficient in syncytium formation. Compared with wild-type ST, the env protein of a molecularly cloned cytopathic ST variant, designated HIV-2/ST/24.1C#2, cased more efficient syncytium formation in the human T-cell line Sup T1, in which the variant was originally generated by repeated passage(Mulligan et al., 1992).
- Human immunodeficiency virus type 2 (D205 ISOLATE) (Website 53):
- Common Name: Human immunodeficiency virus type 2 (D205 ISOLATE)
- GenBank Taxonomy No.: 11710
- Parents: Human immunodeficiency virus
- Description: It has been suggested that the human immunodeficiency virus type 2 (HIV-2) and the simian immunodeficiency virus from rhesus macaques (SIV-mac) evolved from the sooty mangabey virus (SIV-sm). We now describe an HIV-2-related isolated, HIV-2 D205 from a health Ghanaian woman that is genetically equidistant to the prototypic HIV-2 strains and to SIV-sm and SIV-mac. Supported by the observation that HIV-2 D205 differs in a step of envelope glycoprotein processing, our data indicate that it could represent an alternative HIV-2 subtype and that viruses of the HIV-2 / SIV-sm / SIV-mac group could have already infected humans before HIV-2 and SIV-sm / SIV-mac diverged(Dietrich et al., 2002).
- Human immunodeficiency virus type 2 (EHOISOLATE) (Website 54):
- Common Name: Human immunodeficiency virus type 2 (EHOISOLATE)
- Parents: Human immunodeficiency virus
- Description: HIV-2 EHO was initially isolated from peripheral blood lymphocytes of a patient from Ivory Coast with full-blown AIDS. This isolate manifested tropism for stimulated normal human lymphocytes and to neoplastic lymphoid or monocytoid (U937) cell lines. The affinity of HIV-2 EHO particles to bind soluble CD4 molecules was found to be severalfold higher compared to HIV-2 ROD(Rey-Cuille et al., 1994).
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Lifecycle Information
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- Stage Information:
- Immature Virion:
- Size: 100 nm in diameter
- Shape: Budding particles are much more rigid than mature particles, which often have a wrinkled envelope. As the budding process proceeds, one sees progressively more and more of a thin zone of electron density situated under the portion of the cells unit membrane that is being usurped by the developing virus. Simultaneously with the budding, spikes (gp 120) are being inserted into the membrane and appear on the surface of the developing virion envelope. This budding process continues until the virus has formed a complete sphere, i.e., the immature particle
- Mature HIV particle:
- Size: 100 nm in diameter
- Shape: Morphologically, HIV, like all of the Lentiviruses or slow viruses, has an asymmetric core, whose appearance depends on the plane of sectioning. The conical capsid in the mature HIV particle has an electron-dense broad end and a hollow tapered end. Depending on where the core is sectioned and its orientation in the field of view, one sees a hollow or dense spherical structure, when it is cut in cross section, or degrees of foreshortening of the conical core in tangential sections
- Progression Information:
- Maturation:
- From Stage: Immature Virion
- To Stage: Mature HIV particle
- Picture(s):
- Description: Details on the sequence of events during HIV-1 assembly and maturation first emerged from electron microscopy studies. Large Gag complexes were visualized under the plasma membrane followed by the appearance of the spheres connected to the cell by a thin stalk. The nascent immature virions contained an electrondense layer under the lipid envelope and had a doughnut-shaped appearance. The maturation process changed the arrangment of the structural components inside the virion: the radially arranged Gag molecules were dismantled, and a conical core structurewas assembled in the center of the viral particle. It now appears that in immature HIV-1 particles Gag polyprotein is radially arranged under the virus membrane, the N termini lie at the membrane and the C termini extend toward the center of the particle. The MA domain is tightly associated with the inner face of the viral membrane and separated from the capsid layer by a low density region corresponding to its C terminus. Such organization of the MA layer stabilizes the viral membrane. The CA and NC domains form regular layers which contribute to the radial density to the immature particle. According to the generally accepted view, structural changes coupled with virus maturation are induced by proteolytic processing of Gag p55 by the viral protease during or after budding of the virus particles. As with all retroviruses, HIV-1 protease is an aspartic protease and is functional only as a dimer. Activation of protease is a critical step in HIV-1 morphogenesis. Cleavage of Gag and Gag-Pol precursors is necessary for virus maturation and infectivity, and mutation or inhibition of protease abolishes production of infectious virus. It is widely accepted that the cleavage of Gag p55 induces major structural rearrangements in the virus particle, and that the last step of cleavage between CA and p2 triggers the condensation of NC and the RNA genome into a cone-shape core whileCAforms the shell. This rearrangement is necessary for virus infectivity(Bukrinskaya, 2004).
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Genome Summary
- Genome of Human immunodeficiency virus(Website 55)
- Description: INTIAL SEQUENCE DESCRIPTION: A number of different recombinant DNA clones of HTLV-III/LAV have been obtained and analyzed by restriction enzyme digestion and/or nucleotide sequencing. This work has demonstrated that the viral genome is 9182-9213 nucleotides in length, with long terminal repeats (LTRs) of 636-637 nucleotides, and at least seven genes. Three replicative genes include gag, pol, and env, which are similar to those in other retroviruses, though env is longer than that of other retroviruses. A fourth gene, designated tat, is structurally distinct from that of other retroviruses, and encodes a trans-acting factor capable of enhancing virus expression in a positive feedback manner. A fifth gene has recently been identified, and has been named art or anti-repressor of transactivation or trs or trans-repressor of splicing. Two additional genes, designated short open reading frame (sor) and 3 open reading frame (3'orf) are also unique to HTLV-III/LAV, but the functions of their gene products are unknown. An additional open reading frame, designated R, is also presumed to encode a protein product based on the finding of antibodies in infected individuals reactive to these sequences expressed in E. coli(Ratner et al., 1987).
- HIV-1(Website 55)
- GenBank Accession Number: NC_001802
- Size: 9181bp(Website 55).
- Gene Count: 9(Retroviruses, 1997).
- Description: OVERVIEW: Most replication competent retroviruses depend on three genes: gag, pol and env : gag means "group-antigen", pol represents "polymerase" and env is for "envelope". The "classical" structural scheme of a retroviral genome is: 5'LTR-gag-pol-env-LTR 3'. The LTR ("long terminal repeat") regions represent the two end parts of the viral genome that are connected to the cellular DNA of the host cell after integration and do not encode for any viral proteins. The gag and env genes code for the nucleocapsid and the glycoproteins of the viral membrane; the pol gene codes for the reverse transcriptase and other enzymes. In addition, HIV-1 contains in its 9kB RNA six genes (vif, vpu, vpr, tat, rev and nef) that contribute to its genetic complexity. Nef, vif, vpr and vpu were classified as accessory genes in the past, as they are not absolutely required for replication in vitro. However, the regulation and function of these accessory genes and their proteins have been studied and characterized in more detail within the last years(Kamps and Hoffman, 2003). DESCRIPTION OF PROTEINS - gag: (336-1836) The gag region encodes Pr55 Gag. Pr55 Gag is myristylated at the 2Gly position. Proteolytic processing cleaves p17 MA, p24 CA, p7 NC and p2 from Pr55 Gag(Retroviruses, 1997). pol: (2102-4640) The pol ORF is in-frame with the pro ORF; pol gene products are synthesized as part of the Pr160 Gag-Pro-Pol polyprotein. RT is a p66/p51 heterodimer, the two subunits of which differ by the presence or absence of most of the RNase H domain. P32 IN is cleaved from the carboxy-terminal region of Pr160 Gag-Pro-Pol. Integration of HIV-1 DNA produces a 5-bp duplication of flanking cellular DNA(Retroviruses, 1997). vif: (4587-5163) The p23 Vif protein is translated from a singly spliced mRNA(Retroviruses, 1997). vpr: (5105-5339) The p15 Vpr protein is translated from a singly spliced mRNA. Vpr is found at the inner face of the cell membrane in infected cells. Large amounts of Vpr are packaged in virions, although it is not a structural protein(Retroviruses, 1997). tat: (5377-5991, 7925-7968) The p14 Tat protein is translated from multiply spliced mRNAs. Tat is localized in the nucleus of infected cells and activates viral transcription by binding to the TAR region of R. Tat is active as a homodimer and is phosphorylated in its carboxy-terminal region, although the functions of this modification is not known(Retroviruses, 1997). rev: (5516-5591, 7925-8197) The rev ORF spans exons 2 and 3 of a multiply spliced mRNA and encodes the Rev protein (p19). Rev localizes in the nucleus and is phosphorylated on serine residues. Rev binds the RRE (bases 7315-7548) present in intron-containing RNAs, facilitating mRNA transport to the cytoplasm(Retroviruses, 1997). vpu: (5608-5854) The vpu ORF is expressed from a weak initiation (AUG) codon upstream of the env AUG and encodes p16 Vpu. Vpu is phosphorylated on serine residues and localizes to the plasma cell membrane, but is not found in virions(Retroviruses, 1997). env: (5771-8339) The env ORF encodes the gPr160 Env polyprotein precursor that is processed by cellular proteases to generate mature gp120 SU and gp41 TM. The SU protein contains alternating conserved and variable (V) regions. SU mediates HIV-1 adsorption through the coordinate binding to host cell CD4 molecules and to one of several host cell coreceptors. Although the env genes of HIV1 have been extensively sequenced, the only known HIV env structure is the coiled-coil region of TM. The SU/TM pair is thought to form trimers on the virion membrane. There are 24 sites for N-linked glycosylation in SU. There are seven glycosylation sites in TM(Retroviruses, 1997). nef: (8343-8710) The nef ORF lies immedioately downstream from the env ORG and extends into the U3 region of the 3 LTR. P27 Nef is translated from a multiply spliced subgenomic mRNA. It undergoes posttranslational myristylation at the 2 Gly position which helps to localize Nef to the inner aspect of the cell membrane. Nef forms homodimers and is phosphorylated at 15Tyr(Retroviruses, 1997).
- Picture(s):
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Human immunodeficiency virus 1, complete genome (Website 55)
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Human immunodeficiency virus 1, complete genome (Website 55)
- Genome of Human immunodeficiency virus type 2(Website 56)
- Description: Human immunodeficiency virus type 2 (HIV-2) shares many of the same biological properties with the well-studied HIV-1. Both are associated with acquired immunodeficiency syndrome (AIDS) in humans, are cytopathic in tissue culture, and have a tropism for CD4+ subset of T cells, macrophages, and other cells. Concordantly, their genome organization is quite similar and unique among retroviruses. The common feature of HIV genomes is the abundance of open reading frames (ORFs) not found in other retroviruses. In addition to three structural genes (gag, pol, env), there are several extra ORFs. ORFs designated as vif, vpr, tat, rev, and nef are common to HIV-1 and HIV-2. functional analyses of the HIV-1 genome have revealed the functions of these ORFs. In spite of the structural similarity of the genome, the nucleotide sequences and predicted amino acid sequences of these two viruses differ significantly, and furthermore, there is an unique ORF in each virus (vpu, unique to HIV-1, and vpx, unique to HIV-2)(Shibata et al., 1990). Nucleotide sequence comparison between HIV-1, HIV-2 and SIV has revealed the presence of an open reading frame (ORF) in the central region of the genomes of HIV-2 and SIV that has no counterpart in HIV-1. This new ORF, called vpx, is highly conserved between HIV-2ROD and SIVmac. Using anti-peptide sera to the predicted protein and site-directed mutagenesis, we show that mutations in the vpx ORF eliminate the synthesis of a 16 kd protein in HIV-2 infected cells, confirming that this protein is the product of this gene. Full-length clones of HIV-2 containing these mutations are infectious in two permanent T lymphocytic cell lines and two monocytic cell lines. In contrast, we show that loss of VPX function results in a severe defect in the productive infection of human peripheral blood lymphocytes both in the amount of reverse transcriptase activity produced and in core protein expression. These findings suggest that the VPX protein plays an important role in the in vivo life cycle of the HIV-2/SIV viruses(Guyader et al., 1989). Antibody reactivity to the orf-x product was detected in 35 of 42 HIV-2 positive serum samples and 11 of 52 SIV seropositive monkeys. No such antibodies were detected in HIV-1 positive donors, blood donors seronegative for both HIV-2 and HIV-1, or SIV seronegative monkeys. This suggests that orf-x is dispensable for in vitro replication of SIVMAC and that the orf-x gene product of HIV-2 or its antibody can be used to distinguish HIV-2 from HIV-1 infection(Yu et al., 1988).
- HIV-2(Website 56)
- GenBank Accession Number: NC_001722
- Size: 10359bp(Website 56).
- Gene Count: 9(Website 56).
- Description: Infectious molecular clones of the human immunodeficiency virus type 2 (HIV-2) will be valuable tools for the study of regulatory gene functions and the development of an animal model for the human acquired immunodeficiency syndrome (AIDS). To this end, we have cloned and sequenced a novel HIV-2 isolate, HIV-2BEN. One clone, designated MK6, is infectious for various human T-cell lines and for human and macaque peripheral blood lymphocytes (PBL), allowing molecular studies of HIV-2 infection and replication. Since MK6 is highly cytopathic in MT-2 and Molt-4 clone 8 cells, antiviral agents and neutralizing sera may be tested(Kirchhoff et al., 2002).
- Picture(s):
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Human immunodeficiency virus 2, complete genome (Website 56)
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Human immunodeficiency virus 2, complete genome (Website 56)
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Biosafety Information
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Biosafety information for Human immunodeficiency virus
- Level: 2 and 3(US Department of Health Services, 1999).
- Applicable: HIV has been isolated from blood, semen, saliva, tears, urine, cerebrospinal fluid, amniotic fluid, breast milk, cervical secretion, and tissue of infected persons and experimentally infected nonhuman primates. CDC has recommended that blood and body fluid precautions be used consistently when handling any blood-contaminated specimens. This approach, referred to as "universal precautions," precludes the need to identify clinical specimens obtained from HIV-positive patients or to speculate as to the HIV status of a specimen(US Department of Health Services, 1999).
- Precautions: BSL-2 standard and special practices, containment equipment and facilities are recommended for activities involving all blood-contaminated clinical specimens, body fluids and tissues from all humans, or from HIV- or SIV-infected or inoculated laboratory animals. Activities such as producing research-laboratory-scale quantities of HIV or SIV, manipulating concentrated virus preparations, and conducting procedures that may produce droplets or aerosols, are performed in a BSL-2 facility, but using the additional practices and containment equipment recommended for BSL-3. Activities involving industrial-scale volumes or preparation of concentrated HIV or SIV are conducted in a BSL-3 facility, using BSL-3 practices and containment equipment. Nonhuman primates or other animals infected with HIV or SIV are housed in ABSL-2 facilities using ABSL-2 special practices and containment equipment. In the laboratory, the skin (especially when scratches, cuts, abrasions, dermatitis, or other lesions are present) and mucous membranes of the eye, nose, and mouth should be considered as potential pathways for entry of these retroviruses. Whether infection can occur via the respiratory tract is unknown. The need for using sharps in the laboratory should be evaluated. Needles, sharp instruments, broken glass, and other sharp objects must be carefully handled and properly discarded. Care must be taken to avoid spilling and splashing infected cell-culture liquid and other virus-containing or potentially infected materials(US Department of Health Services, 1999).
- Disposal: Studies have shown that HIV is inactivated rapidly after being exposed to commonly used chemical germicides at concentrations that are much lower than used in practice. Embalming fluids are similar to the types of chemical germicides that have been tested and found to completely inactivate HIV. In addition to commercially available chemical germicides, a solution of sodium hypochlorite (household bleach) prepared daily is an inexpensive and effective germicide. Concentrations ranging from approximately 500 ppm (1:100 dilution of household bleach) sodium hypochlorite to 5,000 ppm (1:10 dilution of household bleach) are effective depending on the amount of organic material (e.g., blood, mucus) present on the surface to be cleaned and disinfected. Commercially available chemical germicides may be more compatible with certain medical devices that might be corroded by repeated exposure to sodium hypochlorite, especially to the 1:10 dilution(MMWR, 1987).
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Culturing Information
- Plasma Culture Assay :
- Description: The quantitative plasma culture assay measures the amount of cell-free infectious HIV in patient plasma - a measure of plasma viremia. The assay is similar in design to that used for quantitative PBMC culture. Each sample of patient plasma is cultured with stimulated HIV-negative donor PBMC for 14 days. The assay is performed in duplicate in a 24-well tissue culture plate with 6 fivefold dilutions of plasma. Supernatant from each individual well is assayed by the standard p24 EIA method to determine positivity and level of produced viral protein. The assay utilizes plasma from citrate heparinized peripheral blood (10 ml). For best results, blood should be processed within 4 to 6 h of draw. Plasma not assayed immediately should be stored at -70C for future use(Hammer et al., 1993). Plasma was obtained by centrifugation of blood at 3000xg for 15 minutes which is sufficient to remove all cells. Decreasing volumes of plasma were cultured with 2x10(6) phytohemagglutinin-activated PBMC from healthy blood-bank donors in 1.5 ml of RPMI-1640 medium with 15 percent fetal-calf serum and 10 percent (vol/vol) interleukin-2. Twenty-four hours later all cultures were washed four times with medium. Cocultures were subsequently monitored for the presence of p24 antigen in supernatant fluid, twice weekly for up to 28 days(Ho and Moudgil, 1989).
- Medium: Decreasing volumes of plasma were cultured with 2x10(6) phytohemagglutinin-activated PBMC from healthy blood-bank donors in 1.5 ml of RPMI-1640 medium with 15 percent fetal-calf serum and 10 percent (vol/vol) interleukin-2(Ho and Moudgil, 1989). For the HIV-1 enhanced detection assay, PBMC were resuspended at a concentration of 10(6) cells/ml in RPMI 1640 medium (Sigma, St. Louis, Mo.) supplemented with 10% heat inactivated fetal calf serum (Sigma), penicillin (50 U/ml), streptomycin (50 mg/ml), L-glutamine (2 mM), HEPES buffer (10 mM), and 100 U of recombinant human interleukin-2 (Hoffmann-La Roche, Nutley, N.J.) per ml(Tremblay et al., 2000).
- Optimal Temperature: Cell cultures were incubated at 37C in a humidified 5% CO2 atmosphere(Tremblay et al., 2000).
- Optimal Humidity: Cell cultures were incubated at 37C in a humidified 5% CO2 atmosphere(Tremblay et al., 2000).
- Peripheral Blood Mononuclear Cell Assay :
- Description: HIV can be cultured from the peripheral blood of virtually all HIV-seropositive patients. However, the number of infected cells in the peripheral blood can vary(Hammer et al., 1993). PROCESSING OF DONOR AND PATIENT PBMCs: 1. Centrifuge anticoagulated blood at 200 x g for 10 minutes at 20 to 24C and remove most of the plasma which should be aliquoted and frozen. 2. To one part centrifuged blood, from which most of the plasma has been removed, add one part diluent (saline or PBS) e.g., 8 mL centrifuged blood to 8 mL diluent. 3. Layer 4 parts of diluted blood over 3 parts lymphocyte separation solution (LSS: Organon or Pharmacia) e.g., 16 mL diluted blood over 12 mL LSS. 4. Centrifuge at 400 x g for 30 minutes at 20 to 24C. Remove PBMCs and wash twice in two volumes of PBS or Hanks BSS. 5. Enumerate cells and adjust sample with culture medium to achieve a concentration of 2 million cells per mL. STIMULATION OF DONOR PBMCs: 1. Stimulation Medium for donor PBMCs: a. RPMI 1640 with glutamine; 20% fetal bovine serum (heat-inactivated); PHA-P (5 ttg/mL, Difco or Sigma); 3% IL-2 (Cellular Products, Electro-Nucleonics, or Boehringer Mannheim); penicillin (100 units/mL)/streptomycin (100 t1g/mL) or gentamicin (50 sg/mL). 2. IL-2 should be a purified, delectinated human preparation, not a recombinant product. Amphotericin B should be avoided as it may inhibit HIV replication. 3. Do not use frozen donor cells or pooled donor PBMCs. 4. Process random donor buffy coats within 12 hours of collection. 5. Maximum PBMC concentration in stimulation culture: 2 million PBMCs/mL. 6. Use only anti-HIV negative donors; culture donor PBMCs separately to verify absence of HIV infectivity.C. HIV COCULTURE PROCEDURE: 1. Coculture Medium for HIV isolation - a. RPMI 1640 with glutamine; 20% fetal bovine serum (heat-inactivated); 5%natural, delectinated IL-2; penicillin/streptomycin or gentamicin (concentrations cited above). 2. Coculture patient PBMCs within 8 hours of processing.3. Sediment 1 to 3 day old stimulated donor PBMCs at 200 x g for 10 minutes at 20 to 24C, remove and discard supernatant, then resuspend cells in coculture medium and enumerate cells. Adjust sample with coculture medium to a concentration of 2 million PBMCs/mL. 4. Maintain equivalent concentrations of donor PBMCs to patient PBMCs e.g., 10 million donor cells to 10 million patient cells in 10 mL medium (final PBMC concentration: 2million PBMCs/mL). 5. Remove one-half volume of coculture medium every 3 to 4 days and replace with an equal volume of fresh medium. The medium is saved at -30C to -80C for HIV p24 antigen determination. 6. Once a week add 10 million, freshly pelleted and enumerated, 1 to 3 day old PHA-stimulateddonor cells (2 million PBMCs/mL), resuspended in coculture medium.D. ASSAYING MEDIUM FOR HIV (p24) ANTIGEN TO DETERMINE HIV REPLICATION: I. Fresh or frozen medium may be tested and clarification is optional(Hollinger et al., 1992).
- Medium: All laboratories but one used RPMI 1640 medium containing glutamine and 10 to 20% heat-inactivated fetal bovine serum. Donor PBMCs should be obtained from the buffy coat of random, seronegative donors and processed within 12 h of collection. A delay of 24h is inadvisable, because recovery is then suboptimal(Hollinger et al., 1992). The assay utilizes heparinized or citrated peripheral blood (20 ml), from which PBMC are isolated by a Ficoll-Hypaque gradient. Blood must be processed within 24 h, and cells not used in the assay are to be frozen in liquid nitrogen(Hammer et al., 1993).
- Optimal Temperature: After 2 to 4 days in culture at 37C(Jackson et al., 1988).
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Epidemiology Information:
- Outbreak Locations:
- FIRST PUBLISHED REPORT: In the period October 1980-May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. Two of the patients died. All 5 patients had laboratory-confirmed previous or current cytomegalovirus (CMV) infection and candidal mucosal infection(Gottlieb et al., 1981). Pneumocystis pneumonia in the United States is almost exclusively limited to severely immunosuppressed patients. The occurrence of pneumocystosis in these 5 previously healthy individuals without a clinically apparent underlying immunodeficiency is unusual. The fact that these patients were all homosexuals suggests an association between some aspect of a homosexual lifestyle or disease acquired through sexual contact and Pneumocystis pneumonia in this population. All 5 patients described in this report had laboratory-confirmed CMV disease or virus shedding within 5 months of the diagnosis of Pneumocystis pneumonia(Gottlieb et al., 1981). All the above observations suggest the possibility of a cellular-immune dysfunction related to a common exposure that predisposes individuals to opportunistic infections such as pneumocystosis and candidiasis. Although the role of CMV infection in the pathogenesis of pneumocystosis remains unknown, the possibility of P. carinii infection must be carefully considered in a differential diagnosis for previously healthy homosexual males with dyspnea and pneumonia(Gottlieb et al., 1981).
- PRISONS: According to a national survey of jails and prisons, compared to the genereal population, rates of human immunodeficiency virus (HIV) infection among incarcerated individuals are 8 to 10 times higher. In the 1980s and 1990s, the HIV and crack cocaine epidemics and high rates of incarceration associated with the war on drugs had a devastating and synergistic impact on the physical and mental health of families in urban neighborhoods in the United States. Within public health, the rapid expansion of the correctional system can also have unintended consequences. Initiating antibiotic treatment for tuberculosis, HIV, or other sexually transmitted diseases without adequate follow-up to ensure completion of treatment can lead to the development of drug resistance, a peril to the community as a whole(Freudenberg et al., 2001). On June 30, 1997, more than 6300 state/federal prison inmates and more than 2800 jail inmates had AIDS. Also, there were more than 2600 state/ federal prison releasees and more than 36 000 jail releasees with AIDS in 1997. Thus, almost 16% of the estimated total of 247 000 persons living with AIDS in the United States in 1997 passed through a correctional facility that year(Hammet et al., 2002).
- INJECTION DRUG USERS: Despite a rigorous seroepidemiological surveillance program, only 31 HIV-1-infected individuals were identified in Kaliningrad in the time period of 1988 to June 1996. The yearly incidence rate from 1988 - 1995 in the region was from 0 to 0.09 per 10 000 calculated for the total population. In July 1996, a rapid increase in monthly new HIV-1 infections was detected, which continued through the following year. Between 1 July 1996 and 30 June 1997, 1335 newly diagnosed HIV-1-infected individuals (plus 141 who were tested anonymously, total cumulative number 1507) were detected in Kaliningrad. This gives a yearly incidence rate of 6.07 per 10 000 in 1996 (an increase of 6744% compared with 1995) and the incidence for the first 6 months of 1997 was 8.79 per 10 000. Most of the infected individuals were young, over 65% were in the 14 to 25-year age-group, and 20% were aged 14 to 18 years. Amongst 1269 infected individuals who were asked about their possible risk factors for HIV infection, the majority (n = 1208) reported injecting drug use. In 47 cases the reported risk factor was sexual contact (homo-/heterosexual) and 14 infected individuals were children born to infected mothers. Individuals were asked about risk factors using a standardized questionnaire; 335 individuals were asked about their transmission risk before testing, and 934 were asked when positive test results were delivered. In addition to the 141 anonymous tests, risk factors could not be determined for 97 individuals. The drug that the majority of the interviewed individuals with the injecting drug use risk factor reported using (> 95%) was a home-made opiate extracted from locally produced or imported poppy stems and heads(Liitsola et al., 1998).
- HEMOPHILIACS: In July l982, three heterosexual hemophilia A patients, who had developed Pneumocystis carinii pneumonia and other opportunistic infections, were reported. Each had in vitro evidence of lymphopenia and two patients who were specifically tested had evidence of T-lymphocyte abnormalities. All three have since died. In the intervening 4 months, four additional heterosexual hemophilia A patients have developed one or more opportunistic infections accompanied by in-vitro evidence of cellular immune deficiency. These additional cases of AIDS among hemophilia A patients share several features with the three previously reported cases. All but one are severe hemophiliacs, requiring large amounts of Factor VIII concentrate. None had experienced prior opportunistic infections. All have been profoundly lymphopenic (1000 lymphocytes/cubic mm) and have had irreversible deficiencies in T-lymphocytes. Clinical improvement of opportunistic infections with medical therapy has been short lived. Two of the five have died. In most instances, these patients have been the first AIDS cases in their cities, states, or regions. They have had no known common medications, occupations, habits, types of pets, or any uniform antecedent history of personal or family illnesses with immunological relevance(MMWR et al., 1982).
- WOMEN IN SOUTHERN US: In 2003, women constituted 28% of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS) cases in the United States; approximately 69% of those cases were among non-Hispanic black women. Heterosexual transmission is now the most commonly reported mode of HIV transmission among women. In North Carolina, black women make up a growing proportion of newly reported HIV infections and, in 2003, the HIV-infection rate for black women in North Carolina was 14 times higher than that for white women. Despite this disparity, few epidemiologic studies have examined HIV transmission among black women in the United States, particularly those residing in southern states. In August 2004, the North Carolina Department of Health (NCDOH) invited CDC to assist in an epidemiologic investigation of HIV transmission among black women in North Carolina. This report summarizes the results of that investigation, which indicated that the majority of HIV-positive and HIV-negative sexually active black women in North Carolina reported HIV sexual risk behaviors. These findings underscore the need for enhanced HIV-prevention strategies in this population(MMWR et al., 2005).
- ASIA: The extensive spread of HIV started late in Asia, compared with the rest of the world. The earliest cases of AIDS were reported from Asia in 1984 and 1985, but the potential for widespread epidemics was not appreciated until the more extensive spread of HIV in Cambodia, India, Burma, and Thailand in the early 1990s. Unfortunately, the lessons of devastation from AIDS in Africa and the Caribbean went unheeded in much of Asia, and success stories of disease prevention at the national level in the region remain few. National adult HIV prevalence varies from near 0% in several countries to almost 3% in Cambodia. But a static map cannot show the time evolution of these epidemicsand therein lie major hints about the future of HIV in the region. Temporally, the countries of Asia can be divided into three categories: (1) those where HIV hit early and hard, and where adult HIV prevalence now exceeds 1% eg, Cambodia, Burma, Thailand, and some states in India; (2) those currently in transition, with HIV epidemics growing noticeably in the past 5 years eg, China, Indonesia, Nepal, and Vietnam; and (3) those having very low levels of infection such as: Bangladesh, Laos, the Philippines, and South Korea. Adult HIV prevalence peaked at roughly 15% in Thailand in 1996 and at 33% in Cambodia in 1998. Prevalence is currently falling in both countries, rather than continuing a steady growth. The reason is that they undertook extensive and intensive prevention campaigns with good coverage, which were focused specifically on reducing risk related to sex work in both clients and sex workers. In both countries, condom use between sex workers and clients increased to more than 90%, and the number of men visiting sex workers was halved (from 20% to 10%). This result then raises the issue of what is likely to happen in the countries in transition such as China, Indonesia, and Vietnam. In the absence of extensive prevention programmes to reduce HIV transmission in at-risk populations (clients and sex workers, injecting drug users, and men who have sex with men), they might be expected to see steadily climbing HIV prevalence(Ruxrungtham et al., 2004).
- THAILAND: Thailand experienced its first case of AIDS in 1984. Approximately 800,000 Thais were infected with HIV in 1995 and 1 million Thais became infected by the year 2000. There have been 5 major epidemic waves: among male homosexuals (started 1984-5), intravenous drug users (started 1988), female commercial sex workers (started 1989), male clients (started 1990), and housewives and the newborn (started 1991). Approximately 96 per cent of HIV-1 infected Thais carried recombinant subtype A/E, the rest carried B'. Nine phase I/II HIV-1 vaccine trial protocols have been or are being tested. A phase III trial of gp120 subtype B/E (AIDSVAX, VaxGen) was started in 1999, a total of 2,500 volunteers will be enrolled, and interim analysis is planned for August 2002. Thai investigators are also participating in pre-clinical development of recombinant BCG and DNA vaccines. Multidisciplinary and multi-level approaches, both by the government and private sectors, have had a positive impact on the HIV epidemic as shown by the declining seroprevalence of HIV infection in Thai male conscripts, and of major sexually transmitted diseases in men. Nevertheless, more effort at the grass roots level is needed to ensure further success and sustainability of the control of the HIV epidemic in Thailand(Ruxrungtham and Phanuphak, 2001).
- INDIA: The HIV pandemic is rapidly spreading in India and has infected more than 4 million individuals. Studies have shown a rapid rise in HIV seroprevalence in high-risk groups like commercial sex workers, patients having STDs and IV drug abusers. However, the Indian epidemic is not only restricted to persons with high-risk behaviour, but has also entered the general population. The first HIV positive Indian was reported in 1992 at the Centre. The occurrence of HIV infection increased from nil in 1986 to 19.9% in 2003. The HIV seropositivity was significantly higher (z = 6.79; P < 0.001) in males (6.9%) than in females (3.3%). It was observed that HIV prevalence was highest in the age group of 25 to 29 years in both sexes(Anvikar et al., 2005).
- UGANDA: The timing and scale of HIV prevalence declines in Uganda were distinct. HIV prevalence nationally among pregnant women peaked in 1991 at 21.1% and by 1998 declined to 9.7%, a decline of 54% apparentin both rural and urban settings. By 2000, prevalence had declined further to 6%. In Kampala and other urban sites, where age-specific data were available, HIV declined most in younger age groups, best reflecting recent incidence, with declines of 75% in 15-to 19-year-olds and 60% in 20- to 24-year olds. We expected to see a similar HIV pattern in neighboring countries, but statistically significant HIV declines were absent in similar data in Kenya, Malawi, and Zambia overall or in the 15 to 24 age cohorts. Uganda provides the clearest example that human immunodeficiency virus (HIV) is preventable if populations are mobilized to avoid risk. Despite limited resources, Uganda has shown a 70% decline in HIV prevalence since the early 1990s, linked to a 60% reduction in casual sex. The response in Uganda appears to be distinctively associated with communication about acquired immunodeficiency syndrome (AIDS) through social networks. Despite substantial condom use and promotion of biomedical approaches, other African countries have shown neither similar behavioral responses nor HIV prevalence declines of the same scale. The Ugandan success is equivalent to a vaccine of 80% effectiveness. Its replication will require changes in global HIV/AIDS intervention policies and their evaluation(Stoneburner and Low-Beer, 2004).
- SOUTH AFRICA: South Africa is in the midst of one of the fastest growing HIV epidemics in the world. In the year 2000, an estimated 40% of deaths in adults aged 15-49 were attributable to AIDS, making it the single highest cause of death in South Africa. In the year 2002, there were more people living with HIV in South Africa than in any other country in the world. Simultaneously, South Africa has been the site of growing alarm at the high levels of rape reported from various sources, and the issues of sexual violence and violence against women in general have gained considerable political importance and visibility. Recent initiatives such as the Global Fund to Fight AIDS, Tuberculosis and Malaria, are making resources to address HIV/AIDS available on an unprecedented scale, and donor enthusiasm for introducing antiretroviral drugs must be met with an equal commitment to strengthening the systems that enable such drugs to be accessible, and which give them broader meaning(Kim et al., 2003).
- ORPHANS: According to a United Nations report published in October 2003, half the new cases of HIV infection that occur across the world each year are among 15-24 year olds. This group, constituting two and a half million people, are the next generation of parents. The situation is particularly catastrophic in sub-Saharan Africa where widespread poverty and underdevelopment already undermine childrens health and well being. It is estimated that 10 million people in this region between the ages of 15 and 24, and up to 45% of pregnant women, are infected. With this recognition of the high prevalence of HIV in pregnant women in parts of sub-Saharan Africa, major efforts have been directed at developing and implementing interventions to prevent mother-to-child transmission. These efforts have been largely successful: antiretroviral medication, caesarean section, and locally appropriate feeding practice can now reduce transmission from 40% to below 10%.4 In sub-Saharan Africa these interventions are unfortunately not widely available, but nonetheless, it is still the minority of children who are infected. Orphaning is increasing in sub-Saharan Africa as rates of adult mortality have started to accelerate. However, by far the largest group of vulnerable young children are those living with an HIV infected mother. In sub-Saharan Africa approximately 70% of infected mothers survive for at least the first five years of their childrens lives, and this number will increase with the rollout of antiretroviral medication. It is known that the early years of life are crucial for a childs development, and it is likely that maternal HIV disrupts the rearing environment, thereby putting these children at risk(Stein et al., 2005).
- LATIN AMERICA: By May 2000, 306 536 AIDS cases were reported to the Pan American Health Organization (PAHO/WHO) from countries in Latin America and Caribbean (LAC). Only 1.8% were paediatric cases and 1.5% were perinatal. Since 1993 the male-to-female ratio has significantly decreased from 3.3 to 2.3 in 1999, but the sex rate varies from 1.5 in the Caribbean to 3.5 in the Andean region. There are important differences in the mode of transmission in the different sub-regions. Whereas 42% of total cumulative AIDS cases were transmitted by homosexual or bisexual contact in the Andean region, only 9 and 11% reported this mode of transmission in the Caribbean and Central America. Transmission by injecting drug use varies widely, with higher rates reported in Brazil (19%) and Southern Cone countries (up to 33.4%) and much lower numbers in other subregions. The dominant mode of transmission varies from country to country, but it is mainly through homosexual and bisexual contacts and injecting drug use in most of Mexico, South America and the Andean countries. In Central America and Brazil, heterosexual transmission plays an increasing and important role for HIV dissemination. Brazil being the largest country and most populated country presents a very different state of epidemics among its population. In the Caribbean basin, the main mode of HIV transmission is by heterosexual sex(Calleja et al., 2002).
- Transmission Information:
- From:
Human, Human immunodeficiency virus , To:
Human, Human immunodeficiency virus
Mechanism: GENERAL: The variability observed among and within routes of HIV exposure depends partly on the viral dose and also on whether the virus is transmitted directly into the blood or onto a mucous membrane. In addition, these differences are influenced by a variety of host factors, including both factors common to all routes of exposure and those unique to sexual transmission(Royce et al., 1997). Host susceptibility depends on viral entry into cells through CD4 and chemokine surface receptors. These cells include CD4 T lymphocytes, T Langerhans cells, and other macrophages. In macaques, virus appears in dendritic cells of the vaginal lamina propria soon after vaginal inoculation with simian immunodeficiency virus (SIV). HIV-receptive cells have been found in the lamina propria of oral, cervicovaginal, foreskin, urethral, and rectal epithelia in other primate models(Royce et al., 1997). A late stage of infection is a strong predictor of infectiousness according to both epidemiologic and biologic data. When the index partner has more advanced HIV infection indicated by symptoms of HIV disease, a diagnosis of the acquired immunodeficiency syndrome (AIDS), CD4 counts below 200 cells per cubic millimeter, or p24 antigenemia sexual partners are at a much higher risk of acquiring infection (relative-risk range, 6.1 to 17.6). Host infectiousness is likely to increase as a function of the concentration of virus in the genital tract. Higher viral loads in the blood have been associated with the transmission of HIV to sexual partners of people with transfusion-acquired infections. Data on viral concentration in blood and semen generally support the epidemiologic inferences about the importance of the stage of infection in the transmission of HIV(Royce et al., 1997). The presence of reproductive tract infections is strongly associated with susceptibility to HIV, even after adjustment for sexual behavior. The prevalence of genital ulcer disease (chancroid, syphilis, or herpes) is associated with an increased relative risk of HIV infection, ranging from 1.5 to 7.0 in both men and women(Royce et al., 1997). The properties of HIV itself may also influence transmission. Subtype E, the most common subtype in Thailand, is reported to have a greater tropism for Langerhans cells than subtype B. This tropism may contribute to the rapid epidemic spread of HIV through Thailand and the high percontact transmission rate observed there. High concentrations of HIV in semen specimens from sub-Saharan Africa may reflect differences among HIV clades in the ability to replicate in vivo. There appear to be phenotypic differences between isolates in blood and those in semen. Nonsyncytia-inducing viral isolates that are macrophagetropic are found early in HIV disease and may be better adapted to spreading than lymphocytotropic organisms. Particular viral-envelope geneticsequences are required for vaginal transmission of chimeric simian-human immunodeficiency viruses. Genotypic differences in the viral envelope in blood as compared with genital specimens have been reported in women. In addition, other phenotypic differences between HIV harvested from blood plasma and that harvested from genital secretions may affect the efficiency of transmission. Antiretroviral drug resistance, for example, appears in cell-free and cell-associated virus in the blood and semen at different times(Royce et al., 1997).
- From:
Human, Human immunodeficiency virus , To:
Human, Human immunodeficiency virus
Mechanism: SEXUAL: Transmission through sexual contact accounts for 75 to 85 percent of the nearly 28 million infections with the human immunodeficiency virus (HIV) that have occurred so far(Royce et al., 1997). On a world-wide scale, the vast majority of new infections are acquired through heterosexual contact. The likelihood of transmission from male to female has been estimated to be as high as 8-fold more likely that from female to male, although the biological basis for this is not fully understood(Hansasuta and Rowland-Jones, 2001). VAGINAL (MALE to FEMALE): Using logistic regression analysis, including gender and controlling for condom use, frequency of intercourse, anal sex, partner's CD4+ cell count and clinical stage, sexually transmitted diseases, genital infections, and contraceptive use, we found that the efficiency of male-to-female transmission was 2.3 (95% confidence interval = 1.1-4.8) times greater than that of female-to-male transmission(Nicolosi et al., 1994). The risk per episode of receptive vaginal exposure is estimated at 0.1% to 0.2%(CDC, 1998). VAGINAL (FEMALE to MALE): The overall probability of female-to-male HIV-1 transmission per sex act was 0.0063, several times higher than has been estimated from studies of HIV-1 serodiscordant couples. Infectivity for uncircumcised men was significantly higher than for circumcised men (0.0128 vs. 0.0051;P=0.04 ). Overall transmission probability estimates ranged from 0.0038 to 0.0122 when different HIV-1 prevalences among sex partners were assumed, and a ~23-fold greater infectivity was seen for uncircumcised men compared with circumcised men, across all HIV-1 prevalences(Baeten et al., 2005). ANAL: U.S. survey and other data suggest that, in terms of absolute numbers, approximately seven times more women than homosexual men engage in unprotected receptive anal intercourse. Research among higher risk subpopulations, including bisexual men, injecting drug users, female sex workers, inner-city adolescents, and serodiscordant heterosexual couples, indicates that persons particularly at risk of being infected by or transmitting HIV are also more likely to practice anal sex. Considering this finding, along with the much greater efficiency for HIV infection as well as lower rates of condom usage, a significant proportion of heterosexual transmission in some populations is due to anal intercourse(Halperin, 1999). The major behavioral risk factors in the transmission of the Human Immunodeficiency Virus (HIV) between homosexual/bisexual men include receptive anogenital exposure to infected ejaculate and a large number of sexual partners. Among the 129 men with infected study partners, only the number of receptive anal exposures, truncated at 100, was significantly associated with infection at the 0.05 level. The risk of infection per outside partner was estimated to be 0.075 (+/- 0.018) when only participants with uninfected primary partners were included in the analysis, but 0.095(+/- 0.018) when the full cohort was used(DeGruttola et al., 1989). The risk for HIV transmission per episode of receptive penile-anal sexual exposure is estimated at 0.1% to 3%(CDC, 1998). ORAL: Although casual contact with saliva remains an insignificant factor, oral sexual contact may now be of increasing importance in the transmission of HIV. Oral sex may be less efficient than needle-sharing or anal intercourse for the transmission of HIV, but its increased use by men who have sex with men (MSM) and its prominence in the sexual activity of crack smokers may increase its contribution to HIV transmission. Based on several different models, the per-partner infectivity of receptive oral intercourse (ROI) was about 1% (range, 0.85% - 2.3%), where per-partner refers to the risk with a given partner, uncontrolled for activity level, and should be distinguished from the risk of a single sex act (per-contact risk). In comparison, the per-partner infectivity of anal receptive intercourse was about 10% (range, 4.2% - 12%). In a modeling study that incorporated the stage of infection, it was estimated that oral sex acts imposed a transmission risk that was one-sixth that of anal sex acts. In an assessment of per-contact risk for transmission associated with four types of homosexual contact, Vittinghoff et al. estimated that the risk for unprotected receptive anal sex (0.24%; 95% CI, 0.05 - 0.43) was eight times the risk for unprotected receptive oral sex (0.03%; 95% CI, 0.01 - 0.18)(Rothenberg et al., 1998). ROLE OF VIRAL LOAD: The mean serum HIV-1 RNA level was significantly higher among HIV-1-positive subjects whose partners seroconverted than among those whose partners did not seroconvert (90,254 copies per milliliter vs. 38,029 copies per milliliter, P=0.01). There were no instances of transmission among the 51 subjects with serum HIV-1 RNA levels of less than 1500 copies per milliliter; there was a significant dose-response relation of increased transmission with increasing viral load. In multivariate analyses of log-transformed HIV-1 RNA levels, each log increment in the viral load was associated with a rate ratio of 2.45 for seroconversion(Quinn et al., 2002).
- From:
Human, Human immunodeficiency virus , To:
Human, Human immunodeficiency virus
Mechanism: INJECTION DRUG USE: The AIDS epidemic among injection drug users (IDUs) in the United States was first recognized in 1981. Through case surveillance conducted by the Centers for Disease Control and Prevention (CDC), IDUs with opportunistic infections (OIs) and poor immune response were identified and classified as cases of what was then known as gay-related immune disease. These early cases among IDUs had significant epidemiologic impact. They provided the first evidence that the disease was not restricted to men who have sex with men (MSM), and raised the possibility that the causal agent was blood-borne and likely transmitted through the reuse of contaminated injection equipment(Metzger and Navaline, 2003). The risk for HIV transmission per episode of intravenous needle or syringe exposure is estimated at 0.67%(CDC, 1998).
- From:
Human, Human immunodeficiency virus , To:
Human, Human immunodeficiency virus
Mechanism: BREASTFEEDING: In this trial, the estimated rate of breast milk HIV-1 transmission was 16.2% during the first 2 years of life. Given an HIV-1 infection rate of 36.7% in the breastfeeding arm, breast milk transmission accounted for 44% of all infant infections among those exposed to breast milk. Because more than one quarter of women in the formula arm admitted to noncompliance with feeding modality, our estimated breast milk transmission rate is an underestimate. Because cumulative HIV-1 infection rates in the 2 arms were significantly different as early as 6 weeks of life, our data suggest that substantial transmission occurs early during breastfeeding. By 6 months, an estimated 75% of all breast milk transmission had occurred, despite ongoing exposure for an average of 1 additional year(Nduati et al., 2000).
- From:
Human, Human immunodeficiency virus , To:
Human, Human immunodeficiency virus
Mechanism: BLOOD TRANSFUSION: The general availability of a safe blood supply is of considerable concern to the bood-banking community, public health practitioners, clinicians, and the public. Approximately 1.5 percent of the U.S. population receives transfusions of blood products donated by an estimated 4 million persons each year, and the transfusion rate in persons over 65 years of age is three to four times this figure. The screening of blood donors for HIV-1 antibodies that now takes place has greatly reduced but not eliminated the risk of HIV-1 transmission by transfusion. Our estimate of this risk was 0.003 percent(Cohen et al., 1989). The risk of viral infection associated with blood transfusion is lower than ever before because of aggressive screening and testing practices. The risks were recalculated based on 2001 repeat donor incidence data collected by the American Red Cross. The calculated risk of HIV infection per 1,000,000 RBC units transfused is 0.82 (1 / 1.2 million units transfused)(Jackson et al., 2003). HIV can be transmitted efficiently through blood transfusions: an estimated 95% of recipients become infected from transfusion of a single unit of infected whole blood(CDC, 1998).
- From:
Human, Human immunodeficiency virus , To:
Human, Human immunodeficiency virus
Mechanism: OCCUPATIONAL: Of 57 healthcare workers with documented occupationally acquired HIV infection, most (86%) were exposed to blood, and most (88%) had percutaneous injuries. The circumstances varied among 51 percutaneous injuries, with the largest proportion (41%) occurring after a procedure, 35% occurring during a procedure, and 20% occurring during disposal of sharp objects. Unexpected circumstances difficult to anticipate during or after procedures accounted for 20% of all injuries. Of 55 known source patients, most (69%) had acquired immunodeficiency syndrome (AIDS) at the time of occupational exposure, but some (11%) had asymptomatic HIV infection. Eight (14%) of the healthcare workers were infected despite receiving postexposure prophylaxis (PEP)(Do et al., 2003). The risk per episode of percutaneous exposure (e.g., a needlestick) to HIV-infected blood is estimated at 0.4% (upper limit of 95% confidence interval [CI] = 0.8%)(CDC, 1998).
- From:
Human, Human immunodeficiency virus , To:
Human, Human immunodeficiency virus
Mechanism: SELF-INOCULATION: We identified seven cases of intentional self-inoculation with HIV-positive material. Of these, six are known to have died, and the median time from HIV diagnosis to death was 71 months. All were white and four were women. Five worked in healthcare settings with access to contaminated sharps; one was a caregiver for family members with AIDS, and one had access to HIV-contaminated material through an HIV-positive friend. Five out of the seven had been diagnosed with depression before the inoculation event, and most hadother diagnosed psychiatric disorders based on medical record review or patient self-report(Kellerman et al., 2004).
- From:
Human, Human immunodeficiency virus , To:
Human, Human immunodeficiency virus
Mechanism: ARTIFICIAL INSEMINATION: A 35-year-old female health worker with some occupational risk for acquisition of HIV-1 infection had an acute infectious mononucleosis-like syndrome. She was in hospital for several days. 3 weeks later, she was positive for HIV-1 antibodies. She initially denied any risk factors in her private life, but later disclosed that 3 weeks before her illness she had unsuccessfully undergone artificial insemination with fresh sperm. Upon notification of the patient's illness, the gynaecologist concerned retested the donor, who had meanwhile seroconverted. Viral RNA from the recipient's serum (collected 12 weeks after the date of insemination) was reverse transcribed and the V3 region was amplified by nested PCR. Nucleotide sequence determination of the amplification product revealed 100% identity with viral sequences from the donor on the nucleotide level which was amplified from the DNA of peripheral blood mononuclear cells(Matz et al., 1998).
- Environmental Reservoir:
- Humans:
- Description: AIDS is unique in human history in its rapid spread, its extent and the depth of its impact. Since the first AIDS case was diagnosed in 1981, the world has struggled to come to grips with its extraordinary dimensions. Now, more than 20 years later, 20 million people are dead and 37.8 million people (range: 34.6 - 42.3 million) worldwide are living with HIV. And still, AIDS expands relentlessly, destroying peoples lives and in many cases seriously damaging the fabric of societies(UNAIDS et al., 2004). Two viruses cause AIDS in humans, HIV-1 and HIV-2. In the light of recent confirmation that SIVcpz is the progenitor of HIV-1, it is not surprising that HIV-1 can readily be transmitted to common chimpanzees (Pan troglodytes). HIV-1 infection of the other species of great apes (gorilla, bonobo, orangutan) has not been reported, though HIV-1 infection of gibbons has been reported. In concordance with the generalization that the primate lentiviruses do not cause disease in their natural hosts, chimpanzees infected with viruses of the HIV-1/SIVcpz group do not develop significant CD4+ T-cell loss or AIDS(Joag, 2000). SIVsmm is the progenitor of HIV-2 and SIVmac, which appear to have arisen due to cross-species transmission to humans and macaques, respectively. SIVmac infection in macaque monkeys is a well-characterized model of AIDS(Joag, 2000). Both HIV-1 and HIV-2 are of zoonotic origin. The closest simian relatives of HIV-1 and HIV-2 have been found in the common chimpanzee (Pan troglodytes) and the sooty mangabey (Cercocebus atys), respectively, and phylogenetic evidence indicates that lentiviruses from these species (SIVcpz and SIVsm, respectively) have been transmitted to humans on at least eight occasions. The current HIV-1 pandemic provides compelling evidence for the rapidity, stealth, and clinical impact that can be associated with even a single primate lentiviral zoonotic transmission event. We document for the first time that humans are exposed to a plethora of primate lentiviruses through hunting and handling of bushmeat in Cameroon, a country at the center of HIV-1 groups M, N, and O endemicity that is home to a diverse set of SIV-infected nonhuman primates. To what extent wild monkey populations in other parts of Africa are also infected with diverse SIVs is unknown. A complete and accurate assessment of all SIV-infected nonhuman primate species is needed, as well as a determination of the virus lineage(s) present in each species. Studies are also needed to determine whether zoonotic transmissions of SIVs from primates other than chimpanzees and mangabeys have already occurred and what clinical outcomes were associated with these infections. Results from these studies will yield critical insights into the circumstances and factors that govern SIV cross-species transmission and thus allow determination of human zoonotic risk for acquiring these viruses(Peeters et al., 2002).
- Survival: IN HUMAN: The median survival [of HIV-1 infected patients] from seroconversion to death was 9.8 years, which is considerably longer than has been expected in African populations. This is also comparable to survival times of around 10 years (ranging from 8.3 to approximately 13 years) reported by cohort studies in industrialized countries prior to the widespread use of antiretroviral therapy(Morgan et al., 2002). IN SYRINGE: At 4C, 50% of all syringes contained viable HIV-1 at 42 days storage, the longest storage duration tested. At room temperature (20C), the last day that syringes with 2uL of infected blood were positive was Day 21, and viable HIV-1 was recovered from 8% of syringes. Above room temperature (27, 32, and 37C), the likelihood of encountering syringes with viable HIV-1 when periods of storage exceeded 1 week decreased to less than 1%. The temperature at which drug injectors are likely to store their used syringes will vary according to climate, season, and circumstances faced by the injector. The survival of HIV-1 in contaminated syringes varied over a range of temperatures, and this may be a factor influencing the syringe-borne transmission of HIV-1(Abdala et al., 2000). LAB STORAGE: A recently developed assay for measuring infectious HIV-1 particles was used to determine the stability of the virus under various storage conditions as well as the effect of commonly used disinfectants. At the optimum pH of 7.1 the half life of the virus ranged from approx. twenty-four hours at 37C to no significant loss over 6 months at -75C. Drying the virus on a glass surface or freezing caused a 5-12 fold and 4-5 fold decrease of activity, respectively. The dried preparations, however, were about as stable as when stored in a buffered solution. A solution of iodine and detergent (2% Jodopax) was the only disinfectant examined which removed all detectable HIV-1 activity. Isopropanol and ethanol were more potent than acetone; however, all three solvents left some viable particles after a 30 min treatment with 70% solutions(Tjotta and Hungnes, 1991).
- Intentional Releases:
- Intentional Release Information:
- Description: Transmission of human immunodeficiency virus type 1 (HIV-1) from a male accused of rape and deliberate transmission of HIV-1 was investigated by sequencing of the HIV-1 pol and gag genes from virus obtained from the male and from the female victim. We found that the male and female shared two distinct genetic variants of HIV-1. In pl7gag the major variant had an unusual, out-of frame deletion of 3 nucleotides which the minor variant lacked. These results indicated that the male had transmitted more than one infectious unit to the female. From this study we concluded that it was highly likely that the HIV-1 strains carried by the male and the female were closely epidemiologically linked(Albert et al., 1994).
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Diagnostic Tests Information
- Immunoassay Test:
- Enzygnost HIV Integral II (Dade Behring Marburg) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Enzygnost HIV Integral II cost $2.07 to $2.70 per test in 2004 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.2%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- Antigen:
- Antibody:
- Genedia HIV Ag-Ab ELISA (Green Cross Life Science) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Enzygnost HIV Integral II cost $0.35 to $0.55 per test in 2004 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.3% [95% CI = 0% - 1.9%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- Antigen:
- Antibody:
- Genscreen Plus HIV Ag/Ab (Bio-Rad Laboratories) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Genscreen Plus HIV Ag-Ab cost $0.62 to $0.68 per test in 2004 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 1.7% [95% CI = 0.6% - 3.9%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- Antigen:
- Antibody:
- Murex HIV Ag/Ab Combination (Abbott/Murex) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Murex HIV Ag/Ab Combination cost $0.80 to $1.20 per test in 2004 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.7% [95% CI = 0.1% - 2.4%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- Antigen:
- Antibody:
- Vironostika HIV Uni-Form II Ag/Ab (bioMerieux) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Vironostika HIV Uni-Form II Ag/Ab cost $1.48 to $1.95 per test in 2004 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 1% [95% CI = 0.2% - 2.9%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- Antigen:
- Antibody:
- Vironostika Uni-Form II plus O (Organon Teknika) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Vironostika Uni-Form II plus O cost $1.50 per test in 1997 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 0.3%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- Enzygnost Anti-HIV-1/2 Plus (Behringwerke) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Enzygnost Anti-HIV-1/2 Plus cost $1.00 per test in 1995 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.3% [95% CI = 0% - 0.9%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- IMx HIV-1 / HIV-2 3rd generation Plus (Abbott) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: IMx HIV-1 / HIV-2 3rd generation Plus cost $3.00 per test in 1995 and was rated as being very easy and suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 2.1% [95% CI = 0% - 3.6%](World Health Organization, 2003).
- False Negative: 0.4% [95% CI = 0% - 1.1%](World Health Organization, 2003).
- HIV EIA (Labsystems) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: The HIV EIA cost $0.60 per test in 1995 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.6% [95% CI = 0% - 1.4%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- UBI HIV-1/2 EIA (United Biomedical) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: UBI cost $1.00 per test in 1994 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 0.3%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- Recombigen HIV-1 and/or HIV-2 EIA (Trinity Biotech) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Recombigen cost $1.70 per test in 1993 and was rated as being less easy and less suitable for use in small laboratories by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.4%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 1.4%](World Health Organization, 2003).
- Western Blot (Diagnostic Kit Insert - Western Blotting):
- Time to Perform: unknown
- Description: The Enzyme-Linked lmmunosorbent Blot Technique (Western Blot), has been used to detect antibodies to Human lmmunodeficiency Virus Type 1 (HIV-l), which has been recognized as the etiological agent of the Acquired lmmunodeficiencv Syndrome (AIDS). The combination of electrophoretic separation of complex mixtures of antigens with the highly sensitive immunoblotting technique has been useful in characterizing the antigenic profile of HIV-1 and describing the immune response to this virus in exposed or infected persons. The Cambridge Biotech HIV-1 Western Blot Kit, when used as directed in this insert, will detect antibodies to HIV-1 when present in human serum, plasma, or urine. The position of bands on the nitrocellulose strips allows this antibody reactivity to be associated with specific viral antigens(Diagnostic Kit Insert - Western Blotting).
- HIVAB HIV-1/HIV-2 (rDNA) EIA (Diagnostic Kit Insert - HIVAB EIA):
- Time to Perform: 1-hour-to-1-day
- Description: The HIVAB HIV-1/HIV-2 (rDNA) EIA was developed to allow the simultaneous detection of IgG and IgM antibodies to HIV-1 and HIV-2 and to identify potentially infectious units of donated blood and plasma. It has been established that repeatedly reactive units of blood and plasma should be eliminated from the blood supply. In the HIVAB HIV-1/HIV-2 (rDNA) EIA, human serum, plasma, or cadaveric serum is diluted in a specimen diluent and incubated with a polystyrene bead coated with Recombinant HIV-1 env and gag and HIV-2 env proteins. Specific antibody present in the sample reacts with the antigens on the coated bead. After removal of the unbound aterials and washing of the bead, specific immunoglobulins remaining bound to the solid phase are detected by incubating the bead-antigen-antibody complex with a solution containing HIV-1 gag and env together with HIV-2 env Recombinant proteins labeled with horseradish peroxidase (HRPO)(Diagnostic Kit Insert - HIVAB EIA).
- False Positive: Specificity based on an assumed zero prevalence of antibody to HIV-1 and/or HIV-2 in random donors (17037 out of 17054) is estimated to be 99.90%* with a 95% confidence interval: 99.83-99.94% (Table II). *In these calculations, one sample of the eighteen total repeatedly reactive specimens was confirmed by Western Blot and has been excluded(Diagnostic Kit Insert - HIVAB EIA).
- False Negative: HIV-1 sensitivity was equivalent to a previously licensed test in a population of 352 AIDS patients with known antibodies (352 out of 352 detected for an estimated sensitivity of 100% with a 95% confidence interval: 99.15 - 100%, Table III). Similarly the HIV-1 sensitivity was equivalent to a previously licensed test for 1042 known positive samples from other groups with ARC, High Risk or clinical status unknown (1042 out of 1042 detected for an estimated sensitivity of 100% with a 95% confidence interval: 99.71 - 100%,(Diagnostic Kit Insert - HIVAB EIA).
- Antigen:
-
HIV-1 env (rDNA)
-
HIV-1 gag (rDNA)
-
HIV-2 env (rDNA)
- Antibody:
- OraQuick (MMWR, 2002):
- Time to Perform: minutes-to-1-hour
- Description: On November 7, 2002, the Food and Drug Administration announced approval of the OraQuick Rapid HIV-1 Antibody Test (OraSure Technologies, Inc., Bethlehem, Pennsylvania) for use by trained personnel as a point-of-care test to aid in the diagnosis of infection with human immunodeficiency virus type 1 (HIV-1). OraQuick is a simple, rapid test that can detect antibodies to HIV in fingerstick whole blood specimens and provide results in <20 minutes. The test has been categorized as moderate complexity under the Clinical Laboratory Improvement Amendments of 1988(MMWR, 2002). OraQuick was reactive with OMT and sera from 97 of 101 HIV-infected subjects and 0 of 100 subjects who were uninfected (sensitivity and specificity, 96 and 100%, respectively). Concordance between serum and oral mucosal transudate (OMT) testing and interobserver concordance (kappa = 1.0, P < 0.001) were 100%(O'Connell et al., 2003). OraQuick HIV-1/2 Rapid HIV-1/2 (OraSure Technologies Inc) cost $4.00-12.00 in 2004 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.4% [95% CI = 1.5% - 0.1%](MMWR, 2002). WITH HAART 0%(O'Connell et al., 2003).
- False Negative: 0% [95% CI = 0.3% - 0%](MMWR, 2002). WITH HAART 4%(O'Connell et al., 2003).
- Antigen:
- Antibody:
- Serodia-HIV (Fujirebio) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: Serodia-HIV (Fujirebio) cost $1.10 in 1988 and was rated as being easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 3.1% [95% CI = 1% - 6.6%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.4%](World Health Organization, 2003).
- PATH HIV Dipstick (PATH) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: PATH HIV Dipstick (PATH) cost less than $1.50 in 1991 and was rated as being easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 1.8% [95% CI = 0.9% - 2.9%](World Health Organization, 2003).
- False Negative: 0.5% [95% CI = 0% - 2.7%](World Health Organization, 2003).
- SUDS Murex HIV-1 Ab test (Murex Corporation) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: SUDS Murex HIV-1 Ab test (Murex Corporation) cost $4.50 in 1991 and was rated as being very easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 24.9% [95% CI = 19.1% - 30.7%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 1.5%](World Health Organization, 2003).
- Serodia-HIV-1/2 (Fujirebio) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: Serodia-HIV-1/2 (Fujirebio) cost $2.80 in 1993 and was rated as being less easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.5%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 1.5%](World Health Organization, 2003).
- SPAN COMBAIDS VISUAL (Span Diagnostics) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: SPAN COMBAIDS VISUAL (Span Diagnostics.) cost $0.40 in 1993 and was rated as being easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.7%](World Health Organization, 2003).
- False Negative: 3.5% [95% CI = 0.5% - 6.5%](World Health Organization, 2003).
- CAPILLUS HIV-1/HIV-2 (Trinity Biotech) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: CAPILLUS HIV-1/HIV-2 (Trinity Biotech) cost $2.20 in 1994 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 1.2% [95% CI = 0% - 2.4%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- Antigen:
- Immunocomb II BiSpot HIV 1 and 2 (PBS Orgenics) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: Immunocomb II BiSpot HIV 1 and 2 (PBS Orgenics) cost $1.70 in 1994 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.3% [95% CI = 0% - 0.9%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- Antigen:
- SPAN COMBAIDS VISUAL (Span Diagnostics) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: SPAN COMBAIDS VISUAL (Span Diagnostics) cost $0.50 in 1994 and was rated as being easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 12% [95% CI = 8.5% - 15.5%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- Antigen:
-
Recombinant protein
-
Synthetic peptides
- HIV TRI-DOT (J. Mitra and Co) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: HIV TRI-DOT (J. Mitra and Co) cost $2.00 in 1996 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.3% [95% CI = 0% - 0.9%](World Health Organization, 2003).
- False Negative: 0.4% [95% CI = 0% - 1.1%](World Health Organization, 2003).
- AccuSpot HIV-1 and 2 (Specialty BioSystems) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: AccuSpot HIV-1 and 2 (Specialty BioSystems) cost $2.50 in 1995 and was rated as being very easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 13.7% [95% CI = 9.9% - 17.5%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- BIONOR HIV-1 and 2 (Bionor) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: BIONOR HIV-1 and 2 (Bionor) cost $2.50 in 1995 and was rated as being very easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 1.2% [95% CI = 0% - 2.4%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- SEROCARD HIV (Trinity Biotech) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: SEROCARD HIV cost $4.00 in 1994 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 2.1% [95% CI = 0.9% - 3.6%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- HIV 1 and 2 DoubleCheck (Orgenics) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: HIV 1 and 2 DoubleCheck cost $2.00 in 1996 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.6% [95% CI = 0% - 1.4%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.4%](World Health Organization, 2003).
- EasiDot HIV/EasiSpot HIV (Nubenco Diagnostics) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: EasiDot HIV/EasiSpot HIV was rated as being very easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 28.7% [95% CI = 23.8% - 33.6%](World Health Organization, 2003).
- False Negative: 4.7% [95% CI = 2.1% - 7.3%](World Health Organization, 2003).
- InstantCHEKTM-HIV 1+2 (EY Laboratories) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: InstantCHEKTM-HIV 1+2 cost $1.00 in 2003 and was rated as being easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 2.4% [95% CI = 1% - 4.8%](World Health Organization, 2003).
- False Negative: 0.6% [95% CI = 0% - 3.5%](World Health Organization, 2003).
- GENIE II HIV-1/HIV-2 (Bio-Rad) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: GENIE II HIV-1/HIV-2 cost $2.55 in 2003 and was rated as being easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.3% [95% CI = 0% - 1.9%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- Efoora HIV Rapid (Efoora Inc) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: Efoora HIV Rapid cost $0.75-$2.60 in 2003 and was rated as being very easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 1.1% [95% CI = 0.7% - 4.4%](World Health Organization, 2003).
- False Negative: 3.8% [95% CI = 1.4% - 8.1%](World Health Organization, 2003).
- Efoora HIV Rapid (Efoora Inc) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: Efoora HIV Rapid cost $0.75-$2.60 in 2003 and was rated as being very easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 1.1% [95% CI = 0.7% - 4.4%](World Health Organization, 2003).
- False Negative: 3.8% [95% CI = 1.4% - 8.1%](World Health Organization, 2003).
- SD Bioline HIV 1/2 3.0 (Standard Diagnostics) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: SD Bioline HIV 1/2 3.0 cost $1.10 in 2003 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.7% [95% CI = 0.1% - 2.4%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- Hema Strip(R) HIV 1/2 (Chembio Diagnostics) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: Hema Strip(R) HIV 1/2 cost $1.85-$2.50 in 2003 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.2%](World Health Organization, 2003).
- False Negative: 1.9% [95% CI = 0.4% - 5.5%](World Health Organization, 2003).
- HIV 1/2 STAT-PAK (Chembio Diagnostics) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: HIV 1/2 STAT-PAK cost $0.75-$1.25 in 2003 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.2%](World Health Organization, 2003).
- False Negative: 2.4% [95% CI = 0.7% - 6.4%](World Health Organization, 2003).
- HIV (1+2) Antibody (Colloidal Gold) (KHB Shanghai Kehua Bioengineering) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: HIV (1+2) Antibody (Colloidal Gold) cost $1.50 in 2003 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.2%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- GENEDIA(R) HIV 1/2 Rapid 3.0 (Green Cross Life Science Corp) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: GENEDIA(R) HIV 1/2 Rapid 3.0 cost $0.93-$1.15 in 2003 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.3% [95% CI = 0% - 1.9%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- DoubleCheckGoldTM HIV 1 and 2 (Orgenics) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: DoubleCheckGoldTM HIV 1 and 2 cost $0.65-$0.70 in 2003 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: Lot A: 4.4% [95% CI = 2.4% - 7.4%] Lot B: 5.4% [95% CI = 3.1% - 8.6%](World Health Organization, 2003).
- False Negative: Lot A: 0.6% [95% CI = 0% - 3.5%] Lot B: 0% [95% CI = 0% - 2.3%](World Health Organization, 2003).
- Ancoscreen (Ancos) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: Ancoscreen (Ancos) cost $10.80-$21.50 in 1989 and was rated as being less easy and less suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 9.6% [95% CI = 4.5% - 17.4%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 2.2%](World Health Organization, 2003).
- IFA anti-HIV-1 (Waldheim Pharmazeutika) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: IFA anti-HIV-1 cost $5.60 in 1991 and was rated as being less easy and less suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.7%](World Health Organization, 2003).
- False Negative: 1.1% [95% CI = 0.2% - 3.1%](World Health Organization, 2003).
- New Lav-Blot-I (Sanofi Diagnostics Pasteur) (World Health Organization, 2003):
- Time to Perform: minutes-to-1-hour
- Description: New Lav-Blot-I cost $11.60 in 1991 and was rated as being easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 3.2%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 1.9%](World Health Organization, 2003).
- HIV-1 Western Blot Kit (Open Tray Procedure) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: HIV-1 Western Blot Kit cost $17.70 in 1993 and was rated as being less easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.3%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 1.5%](World Health Organization, 2003).
- IFA anti-HIV-2 (Waldheim Pharmazeutika) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: IFA anti-HIV-2 cost $6.00 in 1991 and was rated as being less easy and less suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.8%](World Health Organization, 2003).
- False Negative: 1.3% [95% CI = 0.3% - 6.9%](World Health Organization, 2003).
- INNO-LIA HIV-1/HIV-2 Ab (Innogenetics) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: INNO-LIA HIV-1/HIV-2 Ab cost $18.40 in 1989 and was rated as being less easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 2%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 1.4%](World Health Organization, 2003).
- Speedscreen HIV (British Bio-Technology) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Speedscreen HIV cost $17.00 in 1990 and was rated as being less easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 33.6% [95% CI = 25.9% - 42.1%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 0.6%](World Health Organization, 2003).
- Pepti-Lav 1-2 (Sanofi Diagnostics Pasteur) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Pepti-Lav 1-2 cost $21.50 in 1990 and was rated as being less easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.9%](World Health Organization, 2003).
- False Negative: 0.7% [95% CI = 0.1% - 3.6%](World Health Organization, 2003).
- Determine HIV-1/2 (Abbott Laboratories Dainabot) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Determine HIV-1/2 cost $1.20 in 2001 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0.6% [95% CI = 0% - 3.3%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 4.5%](World Health Organization, 2003).
- InstantScreenTM HIV-1/2 (Gen 2) (Gaifar) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: InstantScreen HIV-1/2 (Gen 2) cost $8.00-12.00 in 192.00/'01 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 3%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 10%](World Health Organization, 2003).
- ADVANCED QUALITY Rapid HIV Test (InTec Products) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: ADVANCED QUALITY Rapid HIV Test cost $0.80-$1.20 in 2001 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 2.1%](World Health Organization, 2003).
- False Negative: 1.2% [95% CI = 0% - 6.8%](World Health Organization, 2003).
- MedMira Rapid HIV Test (MedMira Laboratories) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: MedMira Rapid HIV Test cost $3.00 in 2000 and was rated as being easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 2.4% [95% CI = 0.4% - 5.9%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 4.5%](World Health Organization, 2003).
- First Response HIV-1/HIV-2 WB (PMC Medical) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: First Response HIV-1/HIV-2 WB cost $1.15 in 2001 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 1.2% [95% CI = 0.1% - 4.2%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 4.5%](World Health Organization, 2003).
- CAPILLUS HIV-1/HIV-2 (Trinity Biotech) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: CAPILLUS HIV-1/HIV-2 cost $2.20 in 2001 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 2.1%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 4.5%](World Health Organization, 2003).
- Uni-Gold HIV (Trinity Biotech) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Uni-Gold HIV cost $2.34 in 2001 and was rated as being very easy and very suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 2.1%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 4.5%](World Health Organization, 2003).
- SMLX Technologies Diagnostic test (SMLX Technologies) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: SMLX Technologies Diagnostic test was rated as being easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 25.2% [95% CI = 18% - 33%](World Health Organization, 2003).
- False Negative: 37.3% [95% CI = 26% - 49%](World Health Organization, 2003).
- OraScreen HIV Rapid Test (Beacon Diagnostics) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: OraScreen HIV Rapid Test was rated as being easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 1.4% [95% CI = 0% - 5%](World Health Organization, 2003).
- False Negative: 44% [95% CI = 32% - 56%](World Health Organization, 2003).
- SalivaxTM-HIV (ImmunoScience) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: SalivaxTM-HIV was rated as being easy and suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 4% [95% CI = 1% - 9%](World Health Organization, 2003).
- False Negative: 20.6% [95% CI = 11% - 33%](World Health Organization, 2003).
- Wellcozyme HIV 1+2 GACELISA (Murex Biotech) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Wellcozyme HIV 1+2 GACELISA was rated as being less easy and less suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 1% [95% CI = 0% - 5%](World Health Organization, 2003).
- False Negative: 0% [95% CI = 0% - 4.8%](World Health Organization, 2003).
- Calypte HIV-1 Urine EIA, Fc (Calypte Biomedical) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Calypte HIV-1 Urine EIA, Fc cost $3.00-$4.25 in 2002 and was rated as being easy and less suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 0% [95% CI = 0% - 1.8%](World Health Organization, 2003).
- False Negative: 2.2% [95% CI = 0.3% - 7.6%](World Health Organization, 2003).
- Calypte HIV-1 Urine EIA (Recombinant) (Calypte Biomedical) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Calypte HIV-1 Urine EIA (Recombinant) cost $3.00-$4.25 in 2002 and was rated as being easy and less suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: 1.4% [95% CI = 0.3% - 4.2%](World Health Organization, 2003).
- False Negative: 1.1% [95% CI = 0% - 5.8%](World Health Organization, 2003).
- Cambridge Biotech HIV-1 Urine Western Blot Kit (CalypteTM Biomedical) (World Health Organization, 2003):
- Time to Perform: 1-hour-to-1-day
- Description: Cambridge Biotech HIV-1 Urine Western Blot Kit cost $26.00 in 2002 and was rated as being easy and less suitable for small laboratory use by the World Health Organization(World Health Organization, 2003).
- False Positive: NA(World Health Organization, 2003).
- False Negative: 1.1% [95% CI = 0% - 5.8%](World Health Organization, 2003).
- Nucleic Acid Detection Test:
- Procleix (Jackson et al., 2002):
- Time to Perform: 1-hour-to-1-day
- Description: The Procleix HIV-1/HCV Assay is a nucleic acid test (NAT) for the simultaneous detection of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA in plasma. There was 100% sensitivity (23 of 23) for detection of HIV-1 with the Procleix HIV-1/HCV and HIV-1 discriminatory assays in specimens tested neat and 100% (23 of 23) sensitivity with the Procleix HIV-1/HCV Assay in specimens diluted 1:16(Jackson et al., 2002).
- False Positive: 0%(Jackson et al., 2002).
- Other Test:
- ViroSeq (Eshleman et al., 2004):
- Time to Perform: 1-hour-to-1-day
- Description: The ViroSeq HIV-1 Genotyping System (Celera Diagnostics, Alameda, Calif.) is an integrated system for genotyping HIV-1 protease and RT that is cleared by the FDA for clinical use. This system utilizes 9 or 10 DNA primers for analysis: 1 for reverse transcription, 2 for PCR amplification, and 6 or 7 for sequence analysis. FDA-cleared ViroSeq system (version 2.0) performs well for the analysis of genetically diverse non-subtype B and intersubtype recombinant strains. In the present study, genotypes were successfully obtained for 124 (98%) of 126 samples infected with genetically diverse HIV-1. The ViroSeq system has seven sequencing primers, which provide overlapping, bidirectional sequence data over the entire region analyzed. Bidirectional sequence data are useful for resolving sequence ambiguities and for confirming the presence of nucleotide mixtures. Nucleotide mixtures detected in genotyping assays reflect the presence of genetically diverse viral variants present in plasma samples from most HIV-1-infected individuals(Eshleman et al., 2004).
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Infected Hosts Information
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- Human
- Taxonomy Information:
- Species:
- Homo sapiens (Website 57):
- Common Name: Homo sapiens
- GenBank Taxonomy No.: 9606
- Description: The earliest documented case of infection with HIV-1 was identified in a sample stored in 1959 from the city now known as Kinshasa in the Democratic Republic of Congo (DRC). The lack of other good-quality material from early time points in the history of HIV makes it hard to be sure about the precise timing of the human epidemic. An important feature of HIV is its inherent variability, which is a function of both the lack of a proof-reading mechanism in the viral reverse transcriptase enzyme and the rapid replication rate of the virus. Together, these features allow HIV to mutate rapidly and they enable variants that are resistant to drugs or immune responses to emerge under selection pressure. Assuming that the evolutionary behaviour of the virus has been consistent over time, it is possible to use the wealth of available HIV-1 sequence data from viruses with known dates of sampling to model virus diversification and to estimate the timing of important events in the virus past. In this way, Korber et al. proposed that the main (M) group of HIV-1 strains that are currently infecting the human population began to diversify around 1930. This gives us some idea of the minimum length of time for which HIV has infected humans, but it does not tell us exactly how or when the first ancestral virus infected a human. It seems probable that much of the early evolution of the virus took place in central Africa, particularly in the DRC, as this is the country from which the most diverse range of virus sequences has been recovered. The most probable source of HIV in humans is the inadvertent introduction of a simian immunodeficiency virus (SIV) from a closely related primate species. In 1986, a second retrovirus strain, known as HIV-2 and having approximately 4060% homology with HIV-1, was isolated from patients with AIDS from West Africa. Careful studies of HIV-2 genomes showed that there is a remarkably close relationship between HIV-2 and SIV strains that infect sooty mangabeys (SIVsm) in the same parts of West Africa, and it is now thought that there have been at least three separate entries of SIVsm into the human population. For some time, the origin of HIV-1 was less clear the most closely related viruses were those found occasionally in captive chimpanzees, but these SIVcpz strains had much less homology with HIV-1 than SIVsm did with HIV-2. The mystery was at least partly solved when SIVcpz strains with greater similarity to HIV-1 were discovered in a chimpanzee species whose habitat hadmarked geographical overlap with the regions of central Africa where the M group of HIV-1 is believed to have originated. It is still not clear to what extent chimpanzees are infected with these SIV strains in the wild or exactly how humans first became infected(Rowland-Jones, 2003).
- Infection Process:
- Infectious Dose: The variability observed among and within routes of HIV exposure depends partly on the viral dose and also on whether the virus is transmitted directly into the blood or onto a mucous membrane. In addition, these differences are influenced by a variety of host factors, including both factors common to all routes of exposure and those unique to sexual transmission(Royce et al., 1997),
- Description: Serum levels of HIV-1 RNA of more than 1500 copies per milliliter. There was a significant dose-response effect with respect to both male-to-female transmission and female-to-male transmission (P<0.001). The rate of transmission was zero among the 51 couples in which the HIV-1 positive partner had undetectable serum levels of HIV-1 RNA or less than 1500 copies per milliliter. Among HIV-1 positive partners with serum HIV-1 RNA levels of less than 3500 copies per milliliter, the rate of transmission was 2.2 per 100 person-years, and the rates progressively increased with increasing viral loads, to a maximum of 23.0 per 100 person-years at a level of 50,000 or more copies per milliliter. It is noteworthy that among the 90 instances of transmission, 5.6 percent occurred among couples in which the HIV-1 positive partner had serum HIV-1 RNA levels of 400 to 3499 copies per milliliter, 17.7 percent among couples in which the seropositive partner had levels of 3500 to 9999 copies per milliliter, 40.0 percent among couples in which the seropositive partner had levels of 10,000 to 49,999 copies per milliliter, and 36.7 percent among couples in which the seropositive partner had levels of 50,000 or more copies per milliliter. There was no significant difference between male-to-female and female-to-male transmission rates after the results were adjusted for viral load (P=0.76), and there were no consistent differences between male-to-female or female-to-male transmission rates within strata of viral load(Quinn et al., 2002),
- Disease Information:
- HIV(i.e., HIV infection) :
- Incubation: BEFORE HAART (Highly Active Anti-Retroviral Therapy): Times from seroconversion to symptomatic disease and AIDS among individuals living in the community have been reported only by Morgan et al. in Uganda. This suggests rapid progression: the median times from seroconversion to WHO disease stages 2 and 3 were 25 months (95% CI = 34-30) and 46 months (95% CI = 36-51) months, respectively. Weight loss, minor mucocutaneous disease, severe bacterial infection, chronic diarrhoea, and chronic fever were the main manifestations(Jaffar et al., 2004), WITH HAART (Highly Active Anti-Retroviral Therapy): The results of this collaborative study, involving 13 prospective studies and over 12 000 HIV-1-infected patients, showed that the prognosis of HIV-1 infection in patients starting HAART could be estimated with precision for groups of patients characterised by different levels of CD4 count, plasma viral load, and other prognostic factors. Because all patients were treatment-naive, our results are not confounded by previous antiretroviral therapy, and are relevant to most patients starting HAART at the present time. The prognostic model has strong discriminatory power, with estimated rates of progression to AIDS or death at 3 years ranging from 34% to 50%. The CD4 cell count at commencement of HAART was the most strongly prognostic factor: patients who started HAART with fewer than 200 cells/L were at substantially higher risk of clinical progression than those with higher counts. Viral load at commencement was associated with subsequent clinical progression only if greater than or equal to 100 000 copies/mL. The other factors associated with clinical progression were age 50 years or greater, a prior diagnosis of AIDS, and infection through injection-drug use(Egger et al., 2002),
- Prognosis:
BEFORE HAART: The natural history of HIV-1 is well described in developed countries, where about 1.5 million people infected with HIV-1 are living with HIV/AIDS. Data from 38 cohort studies conducted in Europe on more than 13 000 people infected with HIV-1 with reliably estimated dates of seroconversion before the widespread use of highly active antiretroviral therapy (HAART) have been collated to estimate the median survival of individuals seroconverting at different ages. For those seroconverting between 15 and 24 years of age the median survival time (and 95% confidence interval (CI) was 12.5 years (95% CI = 12.112.9). For those aged 25 - 34, median survival was 10.9 (95% CI = 10.611.3). For those aged 35 - 44 it was 9.1 (95% CI = 8.79.5). And for those aged 45 - 54 years, the median survival was 7.9 (95% CI = 7.48.5). The survival of people in Africa infected with HIV-1 from their date of seroconversion has been reported in only one study. This study was conducted by Morgan et al. in rural south-western Uganda. Among 168 incident cases, who were infected predominately through heterosexual contact and whose median age at seroconversion was 30 years, 44 individuals died. The median survival was estimated as 9.8 years (interquartile range 6.1 less than 10.3 years). This is about 1 year less than the median survival time of HIV-infected people in developed countries who seroconverted between the ages of 25 and 34 years before HAART was widely available. Although based on small numbers, there was some evidence in the Ugandan study that survival varied with age at infection: older patients tended to have shorter survival times. The age-standardized mortality rate of people infected with HIV-1 was 6.7 deaths per 100 person-years (which was 7.9 times higher than that for controls not infected with HIV)(Jaffar et al., 2004), The median time to AIDS was 9.4 years in our Ugandan cohort. This is comparable with cohorts in industrialized countries before the better management of HIV infection, when the median survival to AIDS was around 9 or 10 years but ranged from 5.7 to over 12 years. We found that the median survival from seroconversion to death was 9.8 years, which is considerably longer than has been expected in African populations. This is also comparable to survival times of around 10 years (ranging from 8.3 to approximately 13 years) reported by cohort studies in industrialized countries prior to the widespread use of antiretroviral therapy(Morgan et al., 2002), WITH HAART: The results of this collaborative study, involving 13 prospective studies and over 12,000 HIV-1-infected patients, showed that the prognosis of HIV-1 infection in patients starting HAART could be estimated with precision for groups of patients characterised by different levels of CD4 count, plasma viral load, and other prognostic factors. Because all patients were treatment-naive, our results are not confounded by previous antiretroviral therapy, and are relevant to most patients starting HAART at the present time. The prognostic model has strong discriminatory power, with estimated rates of progression to AIDS or death at 3 years ranging from 3.4% to 50%. The CD4 cell count at commencement of HAART was the most strongly prognostic factor: patients who started HAART with fewer than 200 cells/L were at substantially higher risk of clinical progression than those with higher counts. Viral load at commencement was associated with subsequent clinical progression only if greater than or equal to 100 000 copies/mL. The other factors associated with clinical progression were age 50 years or greater, a prior diagnosis of AIDS, and infection through injection-drug use(Egger et al., 2002),
- Diagnosis Summary: HIV diagnostic tests function either by detecting host antibodies made against different HIV proteins or by directly detecting the whole virus itself or components of the virus (such as the HIV p24 antigen or HIV RNA). The goal of most HIV diagnostic tests is to detect HIV infection as early as possible, thereby decreasing the length of the diagnostic window. Certain HIV diagnostic tests, however, aim to distinguish between recent and longstanding HIV infections. This is done primarily for epidemiological reasons, in order to estimate the incidence of HIV (the frequency at which new HIV infections arise) within a given population. Regardless of the purpose of the HIV diagnostic test or the types of molecules detected by the test, blood in some form (plasma, serum or dried blood spots) is the preferred sample specimen for most HIV diagnostic tests. In addition to facilitating detection of HIV infection, serologic (blood-based) tests also allow for the determination of HIV viral type (HIV-1 or HIV-2), viral subtype, viral load (as measured by viral RNA levels in the blood), HIV drug resistance and how recently the viral infection was contracted. Moreover, blood specimens can be stored over long periods of time and remain fairly stable. Plasma or serum is usually refrigerated or frozen for long-term storage while dried blood spots remain stable at room temperature. The methods used to collect blood specimens from test subjects include venipuncture and finger pricks. These rather invasive approaches for sample collection are not always palatable to the test subject. As a result, several HIV diagnostic tests have been developed that use saliva or urine as the test specimen because saliva and urine collection are far less invasive than blood collection. What is more, urine and saliva collection may present fewer biosafety concerns than blood collection. However, urine- or saliva-based HIV diagnostic tests, while comparable in their sensitivity and specificity to blood tests, do not allow for the additional analyses of the HIV infection that serologic tests do(Iweala, 2004),
- Symptom Information :
- Syndrome -- Primary HIV infection :
- Description: The signs and symptoms of acute HIV-1 infection usually present within days to weeks after initial exposure. The most common signs and symptoms include fever (median maximal temperature, 38.9C), fatigue, rash that is usually maculopapular but may have protean presentations, headache, lymphadenopathy, pharyngitis, myalgia, arthralgia, aseptic meningitis, retro-orbital pain, weight loss, depression, gastrointestinal distress, night sweats, and oral or genital ulcers. The acute illness may last from a few days to more than 10 weeks, but the duration is usually less than 14 days. The severity and the duration of the illness may have prognostic implications; severe and prolonged symptoms are correlated with rapid disease progression. The nonspecific nature of these symptoms presents a major challenge to health care providers and underscores the need to obtain an accurate history of exposure. An evaluation for acute HIV-1 infection should be performed if a patient has signs and symptoms that are consistent with the diagnosis and a history of exposure to a person with known or possible HIV-1 infection. Acute infection should also be considered in persons presenting with a sexually transmitted disease. Some symptoms are particularly suggestive of acute HIV-1 infection in a person with a compatible history of exposure. A morbilliform rash (also described as maculopapular), usually involving the trunk, occurs in 40 to 80 percent of persons with symptomatic acute HIV-1 infection. Rash may be difficult to detect in darkly pigmented people. Histopathological evaluation of the involved skin shows a mononuclear- cell infiltrate of the superficial dermal vessels, consisting mainly of CD4+ cells, and focal lymphocytic vasculitis. An acute meningoencephalitis syndrome has been reported as another presentation of acute HIV-1 infection, and this syndrome should be considered in the differential diagnosis of aseptic meningitis. Mucocutaneous ulceration, which can involve the buccal mucosa, gingiva, palate, esophagus, anus, or penis, is also highly suggestive of acute infection in a person at risk. In a group of 23 persons at risk of HIV infection who were followed every six months and who became infected, 87 percent had symptomatic acute infection, and 95 percent of these patients sought medical evaluation. But only one in four persons in the study received the appropriate diagnosis of acute HIV-1 infection at the first clinic visit, even though there should have been a high index of suspicion. Because the signs and symptoms are nonspecific, acute HIV-1 infection is frequently confused with a variety of other illnesses, including infectious mononucleosis, secondary syphilis, acute infection with hepatitis A or B, roseola or other viral infections, and toxoplasmosis. Acute HIV-1 infection should therefore be included in the differential diagnosis of any unexplained severe febrile illness. The nonspecific symptoms of acute HIV-1 infection make it difficult to determine the true frequency of symptomatic illness in newly infected persons. Estimates of the frequency range from 40 to 90 percent, but these studies have not included control groups. In a recent study in India, 81 percent of persons with acute HIV-1 infection seen at a clinic for sexually transmitted diseases had at least one of the following eight signs or symptoms: fever, adenopathy, joint pain, thrush, pharyngitis, rash, diarrhea, and paresthesia. Laboratory studies performed during the initial infection may show lymphopenia and thrombocytopenia, but atypical lymphocytes are infrequent. The characteristic laboratory findings are not unique to HIV-1 infection but are also observed in other acute viral illnesses. The CD4+ cell count usually decreases during acute HIV-1 infection but may remain in the normal range; typically, over the ensuing weeks, the CD4+ cell count decreases, the CD8+ cell count increases, and the ratio of CD4+ cells to CD8+ cells is inverted. Most persons with acute HIV-1 infection do not expect to receive this diagnosis even if they have had recent risky exposures. Clinicians should take a careful history for HIV-1 exposure and should anticipate that their patients will be anxious and fearful when the diagnosis is entertained. It is essential at this stage to address the patients concerns, explain the planned evaluation, and describe possible treatment options(Kahn and Walker, 1998).
- Symptom -- Fever :
- Symptom -- Headache :
- Symptom -- Fatigue :
- Symptom -- Arthralgia :
- Symptom -- Myalgia :
- Symptom -- Vomiting :
- Symptom -- Diarrhoea :
- Symptom -- Cutaneous rash :
- Symptom -- Inguinal lymphadenopathy :
- Symptom -- Oral thrush / candidiasis :
- Syndrome -- Acquired Immunodeficiency Syndrome (AIDS) :
- Description: The etiologic agent of acquired immunodeficiency syndrome (AIDS) is a retrovirus designated human immunodeficiency virus (HIV). The CD4+ T-lymphocyte is the primary target for HIV infection because of the affinity of the virus for the CD4 surface marker. The CD4+ T-lymphocyte coordinates a number of important immunologic functions, and a loss of these functions results in progressive impairment of the immune response. Studies of the natural history of HIV infection have documented a wide spectrum of disease manifestations, ranging from asymptomatic infection to life-threatening conditions characterized by severe immunodeficiency, serious opportunistic infections, and cancers. Other studies have shown a strong association between the development of life-threatening opportunistic illnesses and the absolute number (per microliter of blood) or percentage of CD4+ T- lymphocytes. As the number of CD4+ T-lymphocytes decreases, the risk and severity of opportunistic illnesses increase.Measures of CD4+ T-lymphocytes are used to guide clinical and therapeutic management of HIV-infected persons. Antimicrobial prophylaxis and antiretroviral therapies have been shown to be most effective within certain levels of immune dysfunction. As a result, antiretroviral therapy should be considered for all persons with CD4+ T-lymphocyte counts of less than 500/uL, and prophylaxis against Pneumocystis carinii pneumonia (PCP), the most common serious opportunistic infection diagnosed in men and women with AIDS, is recommended for all persons with CD4+ T-lymphocyte counts of less than 200/uL and for persons who have had prior episodes of PCP. Because of these recommendations, CD4+ T- lymphocyte determinations are an integral part of medical management of HIV-infected persons in the United States.The revised CDC classification system for HIV-infected adolescents and adults categorizes persons on the basis of clinical conditions associated with HIV infection and CD4+ T- lymphocyte counts. The system is based on three ranges of CD4+ T- lymphocyte counts and three clinical categories and is represented by a matrix of nine mutually exclusive categories. This system replaces the classification system published in 1986, which included only clinical disease criteria and which was developed before the widespread use of CD4+ T-cell testing. 1993 AIDS SURVEILLANCE CASE DEFINITION: Candidiasis of bronchi, trachea, or lungs; Candidiasis, esophageal ; Cervical cancer, invasive; Coccidioidomycosis, disseminated or extrapulmonary; Cryptococcosis, extrapulmonary; Cryptosporidiosis, chronic intestinal(greater than 1 month's duration); Cytomegalovirus disease (other than liver, spleen, or nodes); Cytomegalovirus retinitis (with loss of vision); Encephalopathy, HIV-related; Herpes simplex: chronic ulcer(s) (greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis; Histoplasmosis, disseminated or extrapulmonary; Isosporiasis, chronic intestinal (greater than 1 month's duration);Kaposi's sarcoma; Lymphoma, Burkitt's (or equivalent term); Lymphoma, immunoblastic (or equivalent term); Lymphoma, primary, of brain; Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary; Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary); Mycobacterium, other species or unidentified species, disseminated or extrapulmonary; Pneumocystis carinii pneumonia; Pneumonia, recurrent; Progressive multifocal leukoencephalopathy; Salmonella septicemia, recurrent; Toxoplasmosis of brain; Wasting syndrome due to HIV(CDC, 1992).
- Treatment Information:
- Abacavir (ABC) [Trade name: Ziagen, Trizivir] (Kamps and Hoffman, 2003): The hypersensitivity reaction, though rare, complicates use of abacavir. Abacavir should be prescribed by HIV clinicians! Abacavir is otherwise well tolerated, possibly causing less mitochondrial toxicity than other nucleoside reverse-transcriptase inhibitors (NRTIs), and possibly with a better future. FORMULATIONS: Ziagen : 300 mg tablets; 20 mg/ml oral solutions, 240 ml Trizivir: Tablets containing 300 mg abacavir and 150 mg lamivudine and 300 mg zidovudine DOSE: 300 mg bid. Abacavir can be taken with or without food(Kamps and Hoffman, 2003).
- Contraindicator: Abacavir is contraindicated in cases with previously diagnosed abacavir hypersensitivity and after interruption of therapy, if a prior hypersensitivity reaction (HSR) cannot be ruled out retrospectively. Patients should be well advised on the HSR, but not frightened. With only mild symptoms (see below), abacavir should not be stopped too quickly, as an intercurrent infection may "simulate" the HSR. Therapy may be continued for one or two days under close observation. Rechallenge after suspected HSR is contraindicated, as a repeated allergic reaction can be fatal. Patients should be told to consult a doctor immediately if at least two of the following symptoms occur: fever, shortness of breath, sore throat or cough, rash (erythema and/or pruritus), nausea or vomiting or diarrhea or abdominal pain, extreme fatigue or diffuse pain or general malaise(Kamps and Hoffman, 2003).
- Complication: Abacavir causes a hypersensitivity syndrome (HSR) in ca. 2 to 6 % of patients. This usually occurs within the first six weeks after initiation of treatment. Pruritus and rash are common, but may also be absent. The HSR may present only with fever and slowly developing malaise. Gastointestinal complaints (nausea, vomiting, diarrhea, abdominal pain) and fatigue are also possible, but not necessarily linked to the HSR. Elevated liver function tests, insomnia and dizziness are rare. There is probably a genetic predisposition for the HSR(Kamps and Hoffman, 2003).
- Drug Resistance: Unfortunately, there is cross-resistance to many other nucleoside reverse transcriptase inhibitors (NRTIs)(Kamps and Hoffman, 2003).
- Amprenavir (APV) [Trade name: Agenerase] (Kamps and Hoffman, 2003): Due to the high pill burden, unboosted dosing of amprenavir is hardly acceptable today. The availabilty of the prodrug fos-amprenavir will presumably make this drug more attractive in the future. FORMULATIONS: 50 mg capsules, 150 mg capsules, 15 mg/ml oral solution, 240 ml DOSE: 8 capsules amprenavir bid of 150 mg each (1200 mg bid) or 4 capsules amprenavir bid of 150 mg each (600 mg bid) plus 100 mg ritonavir bid or 8 capsules amprenavir qd of 150 mg each (1200 mg qd) plus 200 mg ritonavir qd(Kamps and Hoffman, 2003).
- Contraindicator: Amprenavir is contraindicated in pregnancy and in children under 4 years; and as concurrent treatment with rifampicin, ergotamines, cisapride, bepridil, pimozide, midazolam and triazolam. Concurrent treatment with amiodarone, warfarin, lidocaine, tricyclic anti-depressants, quinidine, cyclosporine and tacrolimus should be avoided. Amprenavir is not recommended for concurrent treatment with lovastatin, simvastatin, carbamazepine, phenobarbital, phenytoin or sildenafil (Viagra: increased incidence of hypotension, priapism!) Use with caution in patients with a history of sulfonamide allergy. Concurrent treatment with rifabutin: Reduce rifabutin dose by 50%. Amprenavir should be taken at least one hour before or after antacids or didanosine. Dose adjustment (measure plasma levels!) should be considered in combination with lopinavir. Amprenavir solution contains 50 % propylene glycol. It is therefore contraindicated in children less than 4 years old, pregnant women, patients with renal or liver failure, and for concurrent administration with disulfiram or metronidazole(Kamps and Hoffman, 2003).
- Complication: Mostly gastrointestinal with nausea, vomiting, diarrhea, flatulence, tenesmus, perioral paresthesia. Occasionally headache, fatigue; rash in 5-10 % of patients, usually in the second week of treatment. A Stevens-Johnson syndrome is rare (<1 %). In combination with ritonavir, more frequent elevations of cholesterol, triglycerides and transaminases. Lowered glucose tolerance, rarely diabetes mellitus. Lipodystrophy(Kamps and Hoffman, 2003).
- Drug Resistance: When boosted with ritonavir, amprenavir is well suited for salvage therapy because of an interesting resistance profile(Kamps and Hoffman, 2003).
- Atazanavir (AZV) [Trade name: Reyataz] (Kamps and Hoffman, 2003): Atazanavir is the first once-daily protease inhibitor (PI), and has an antiviral potency that should be comparable to nelfinavir. In comparison to boosted PIs, atazanavir is slightly weaker, but has a favorablelipid profile. Whether this will have an effect on lipodystrophy still needs to be shown. FORMULATIONS: 200 mg capsules DOSE: 400 mg qd, with a meal if possible(Kamps and Hoffman, 2003).
- Contraindicator: Concurrent treatment with efavirenz reduces plasma levels of atazanavir. In one study (O'Mara et al. 2002) this was compensated by additional administration of 200 mg ritonavir.Rifabutin has no effect on the pharmacokinetics of atazanavir(Kamps and Hoffman, 2003).
- Complication: Relatively frequent increases in bilirubin, so farnot limiting treatment. Diarrhea in ca. 30 %. In addition: nausea, vomiting, headache, abdominal pain. These complaints usually resolve within the first weeks of treatment. In contrast to other PIs: No dyslipidemia. The effect on lipodystrophy remains unknown(Kamps and Hoffman, 2003).
- Combivir (Kamps and Hoffman, 2003): Combination of Nucleoside reverse transcriptase inhibitors (NRTIs).FORMULATIONS: Tablets containing 150 mg lamivudine and 300 mg zidovudine.DOSE: 1 tablet bid(Kamps and Hoffman, 2003).
- Delavirdine (DLV) [Trade name: Rescriptor] (Kamps and Hoffman, 2003): Delavirdine is rarely used, due to impractical dosing and druginteractions, and it has been completely marginalized by the other two NNRTIs nevirapine and efavirenz. However, the drug has some theoretical potential: It is fairly well tolerated (no hepatotoxicity, no CNS problems), and increases levels of indinavir and saquinavir. If more data was available, delavirdine could be an alternative to ritonavir for boosting. FORMULATIONS: 100 mg tablets, 200 mg tablets DOSE: 400 mg tid(Kamps and Hoffman, 2003).
- Contraindicator: Delavirdine is contraindicated for concurrenttreatment with rifabutin, rifampin, carbamazepine, phenytoin, alprazolam, astemizole, phenobarbital, cisapride, midazolam, terfenadine and triazolam. There is little data on combination with nelfinavir, lopinavir and ritonavir. Amprenavir levels seem to be reduced by delavirdine.Delavirdine interacts with numerous drugs via reduction of CYP3A-activity. It increases the AUC of sildenafil, dapsone, clarithromycin, quinidine and warfarin. Delavirdine levels are lowered by didanosine, H2 blockers, carbamazepine, phenytoin and antacids(Kamps and Hoffman, 2003).
- Complication: Rash, usually occurring within the first six weeks of treatment. In uncomplicated cases, symptomatic treatment with antihistamines. If systemic effects such as fever, conjunctivitis, myalgia and arthralgia occur, delavirdine should be discontinued. Nausea, elevated transaminases(Kamps and Hoffman, 2003).
- Drug Resistance: It has the usual nonnucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance(Kamps and Hoffman, 2003).
- Didanosine (ddI) [Trade name: Videx] (Kamps and Hoffman, 2003): Important, well investigated and frequently used NRTI. Combinationwith stavudine can be problematic as there are cumulative toxicities. Even though once-daily dosing is possible, the drug must be taken on an empty stomach, and many antiretroviral drugs must be taken at intervals before or after didanosine. FORMULATIONS: Buffered tablets: 25 mg, 50 mg, 100 mg, 200 mg; EC capsules: 125 mg, 200 mg, 250 mg, 400 mg; 2 g/100 ml pediatric powder; 4 g/200 ml pediatric powder DOSE: 400 mg qd (body weight > 60 kg) or 250 mg qd (body weight < 60 kg). Didanosine must be taken on an empty stomach, at least 2 hours after or 1 hour before meals(Kamps and Hoffman, 2003).
- Contraindicator: Acute and chronic panreatitis are contraindications caution in patients with alcoholism! If possible, concurrent treatment with drugs can that cause pancreatitis (e.g. intravenous pentamidine) should be avoided. The following drugs should be used with caution: ethambutol, cisplatin, disulfiram, ethionamide, INH, vincristine, etc. (peripheral neuropathy). Concurrent treatment with indinavir, zalcitabine, dapsone, ketoconazole, itraconazole, or tetracyclines should be given 2 hours before or after didanosine. Dose reduction is necessary for concurrent treatment with tenofovir!Initially, monthly monitoring of amylase, blood count, transaminases, bilirubin. Patients should be informed about the risk of pancreatitis. Didanosine should be discontinued if there is clinical suspicion for pancreatitis, with no rechallenge(Kamps and Hoffman, 2003).
- Complication: Diarrhea, nausea, headache, rash. Pancreatitis, even after longer periods on treatment! Peripheral polyneuropathy. Rarely lactic acidosis, especially in combination withstavudine(Kamps and Hoffman, 2003).
- Efavirenz (EFV) [Trade name: Sustiva, Stocrin] (Kamps and Hoffman, 2003): Efavirenz is a frequently used nonnucleoside reverse transcriptase inhibitor (NNRTI), with uncontested antiretroviral potency. It has multiple CNS side effects, for which pathogenesis is not sufficiently understood. Drug interactions have been documented for a variety of drugs commenly prescribed to HIV patients. FORMULATIONS: 50 mg capsules, 100 mg capsules, 200 mg capsules, 600 mg capsules DOSE: 600 mg daily (3 capsules qd of 200 mg each or 1 capsule qd of 600 mg), preferably before going to bed(Kamps and Hoffman, 2003).
- Contraindicator: Contraindicated in pregnancy! Contraindicated for concurrent treatment with ergotamines, astemizole, cisapride, midazolam, terfenadine und triazolam. Should not be combined with contraceptive pills. Should not be given in combination with saquinavir or amprenavir without ritonavir boost (insufficient plasma levels of saquinavir and amprenavir)(Kamps and Hoffman, 2003).
- Complication: Nightmares, confusion, dizziness, somnolence, abnormal thinking, impaired concentration, insomnia, depersonalization. These CNS symptoms usually resolve substantiallyafter a few weeks. A rash (15 %) may also occur in the first weeks, but severe cases of blistering, desquamating and ulceration are rare. Elevation of liver functions and biliary enzymes, especially gammaGT; hypercholesterinemia, hypertriglyceridemia(Kamps and Hoffman, 2003).
- Emtricitabin (FTC) [Trade name: Coviracil] (Kamps and Hoffman, 2003): Emtricitabine is a well tolerated NRTI, comparable to lamivudine in its resistance profile. It can be taken once a day. DOSE: 200 mg qd(Kamps and Hoffman, 2003).
- Indinavir (IDV) [Trade name: Crixivan] (Kamps and Hoffman, 2003): Effective and well-investigated PI, the use of which is slightlylimited due to skin, kidney and intestinal problems. There is multiple cross-resistance to other PIs, but the drug has good CNS penetration. Today, indinavir is generally used with ritonavir boosting, which simplifies dosing. FORMULATIONS: 200 mg capsules, 333 mg capsules, 400 mg capsules DOSE: In combination with ritonavir: 800 mg bid (two 400 mg capsules bid) plus 100 mg ritonavir bid (one 100 mg capsulebid) or 400 mg bid (one 400 mg capsule bid) plus 400 mg ritonavir bid (four 100 mg capsules bid). Without ritonavir boosting: 800 mg tid (two 400 mg capsules tid) one hour before or two hours after meals. Impaired liver function: 600 mg tid (three 200 mg capsules tid)(Kamps and Hoffman, 2003).
- Contraindicator: The concurrent use of rifampicin, astemizole, terfenadine, cisapride, triazolam, ergotamines, simvastatin, lovastatin, or St. Johns wort is contraindicated(Kamps and Hoffman, 2003).
- Complication: Nephrolithiasis (in up to 25 %). Less frequently: nephrotoxicity with elevated serum creatinine. Diarrhea, nausea, vomiting. A sicca syndrome occurs relatively frequently (dry skin, mouth, eyes); ingrown toenails and paronychia; rarely alopecia. Asymptomatic hyperbilirubinemia. Lipodystrophy ("Crixbelly"), dyslipidemia, disorders of glucose metabolism(Kamps and Hoffman, 2003).
- Lamivudine (3TC) [Trade name: Epivir, Combivir, Trizivir] (Kamps and Hoffman, 2003): Well tolerated drug, but rapid development of resistance. Lamivudineis frequently used as a component of the fixed combination tablets Combivir and Trizivir. It is also effective against hepatitis B virus. FORMULATIONS: Epivir: 150 mg tablets; 300 mg tablets, 10mg/ml oral solution, 240 ml; Combivir: Tablets containing 150 mg lamivudine and 300 mg zidovudine; Trizivir: Tablets containing 150 mg lamivudine and 300 mg zidovudine and 300 mg abacavir DOSE: Epivir - 300 mg qd or 150 mg bid; Children receive 4 mg/kg, with a maximum of 150 mg bid. Combivir - 1 tablet bid, containing 150 mg lamivudineand 300 mg zidovudine. Trizivir - 1 tablet bid, containing 150 mg lamivudineand 300 mg zidovudine and 300 mg abacavir.(Kamps and Hoffman, 2003).
- Contraindicator: Lamivudine requires dose adjustmentbased on renal function(Kamps and Hoffman, 2003).
- Complication: Fatigue, nausea, vomiting, diarrhea, headache, insomnia, myalgia and arthralgia may occur, but are usually due to other drugs in the combination (see sections on zidovudineand abacavir). Peripheral polyneuropathy, pancreatitis and lactic acidosis are rare(Kamps and Hoffman, 2003).
- Drug Resistance: Rapid development of resistance(Kamps and Hoffman, 2003).
- Lopinavir (LPV) [Trade name: Kaletra] (Kamps and Hoffman, 2003): Kaletra is a very effective and relatively well tolerated PI. Kaletra is an ideal drug for salvage therapy, as it has astonishing potency in PI-experienced patients with multiple resistance mutations. It remains to be proven whether or not Kaletra is superior to other boosted PIs in the initial therapy. Disadvantages include extremely high lipid levels and drug interactions. FORMULATIONS: Capsules with 133.3 mg lopinavir (LPV) + 33.3 mg ritonavir (RTV); bottles of 180 capsules. Solutions with 80 mg lopinavir + 20 mg ritonavir per ml; bottles of 160 ml. DOSE: 3 capsules bid or 5 ml solution bid with meals In combination with efavirenz or nevirapine, the dose should be increased to 4 capsules bid or 6.5 ml solution bid. Measure plasma levels!(Kamps and Hoffman, 2003).
- Contraindicator: Drug interactions are numerous. All drugs metabolized by the CYP3A or CYP2D6 enzyme systems are contraindicated: flecainide, propafenone, astemizole, terfenadine, ergotamines, cisapride, pimozide, midazolam, triazolam. Rifampicin and St. Johns wort reduce the efficacy of lopinavir. Caution with: lovastatin, simvastatin (myopathy, rhabdomyolysis), carbamazepine, phenobarbital, phenytoin or sildenafil (hypotension), amiodarone, warfarin, lidocaine, tricyclic antidepressants, quinidine, cyclosporine, tacrolimus. Measure plasma levels in patients with reduced liver function tests, especially in cases with concurrent hepatitis B or C or significantly elevated transaminases. If lopinavir is being combined with didanosine, didanosine must be taken one hour before or two hours after lopinavir. Lopinavir solution contains alcohol, therefore no co-medication with disulfiram or metronidazole. Caution with the pill (contraception not safe). When used with rifabutin, the rifabutin dose should be reducedby 75 %, i.e. 150 mg qd every two days. Increasing the methadone dose may be necessary(Kamps and Hoffman, 2003).
- Complication: Mainly diarrhea, nausea, and dyslipidemia. Also: headaches, and elevated transaminases(Kamps and Hoffman, 2003).
- Drug Resistance: Kaletra is an ideal drug for salvage therapy, as it has astonishing potency in PI-experienced patients with multiple resistance mutations(Kamps and Hoffman, 2003).
- Nelfinavir (NFV) [Trade name: Viracept] (Kamps and Hoffman, 2003): A relatively well tolerated and well investigated PI, but is slightly less potent than boosted PIs. A Nelfinavir-based PI regimen is less potent than NNRTI regimens. Main problems include high pill burden and frequent diarrhea. Due to its favorable resistance profile (after failure of nelfinavir treatment, other PIs may still have good efficacy), it is well suited as a first-line PI. FORMULATIONS: 250 mg tablets, 50 mg/g oral powder, 144 g DOSE: 1250 mg bid or 750 mg tid with meals(Kamps and Hoffman, 2003).
- Contraindicator: Contraindicated for co-medication with rifampicin, the pill, astemizole, terfenadine, cisapride, triazolam, ergotamines, simvastatin, lovastatin, and St. Johns wort. In combination with rifabutin: 150 mg rifabutin qd and increase nelfinavir dose to 1000 mg tid. Methadone: If withdrawal symptoms occur, dose may be increased.Sildenafil: maximum 25 mg/48 h(Kamps and Hoffman, 2003).
- Complication: Diarrhea! Meteorism, and nausea also occur.Lipodystrophy, dyslipidemia, reduced glucose tolerance(Kamps and Hoffman, 2003).
- Nevirapine (NVP) [Trade name: Viramune] (Kamps and Hoffman, 2003): Nevirapine is a frequently prescribed NNRTI. As with all NNRTIs, a single point mutation is sufficient to develop a highlevel resistance. Nevirapine is very useful for simplification of successful HAART regimens. It has a good long-term tolerability with a favorable lipid profile. The main problem, besides development of resistance, is hepatotoxicity in the first months of treatment. Nevirapine is effective for prophylaxis of mother-to-child transmission. FORMULATIONS: 200 mg tablets, 10 mg/ml suspension, 240 ml DOSE: 1 tablet bid. Always start with lead-in dosing! The initial lead-in dose (1 tablet/day over two weeks) reduces the frequency of rash. For resumption of treatment after treatment interruption, lead-in dosing is generally not necessary if the drug was well tolerated before. Due to its long half-life, nevirapine should be discontinued three days before other backbone drugs are administered, in order to prevent the development of resistance. Nevirapine may be taken on an empty stomach orwith meals(Kamps and Hoffman, 2003).
- Contraindicator: Cautious use in hepatic dysfunction (measure plasma levels). Contraindicated for co-medication with rifampicin, ketoconazole, St. Johns wort and the pill. Azole derivatives: Fluconazole should be used for antimycotic treatment(Kamps and Hoffman, 2003).
- Complication: Mainly hepatotoxicity, rash. Less frequently: fever, nausea, drowsiness, headache, myalgia. These side effects may occur with or without hepatotoxicity and/or rash. gammaGT isfrequently elevated. To detect hepatotoxicity (occurring in 15 %; defined as an increase in transaminases to at least three times the upper limit of normal), liver function tests should be monitored biweekly for the first two months. Thereafter, monthly tests are necessary, asmore than half of the hepatotoxic epidoses occur after the first quarter of treatment. In cases of hepatotoxicity, treatment must be interrupted until liver function tests have returned to initial levels. Treatment is restarted with 200 mg qd. The dose may be increased to 200 mg bid only after a prolonged period of observation. If liver enyzmes increase again, nevirapine should be permanently discontinued. The website of the EMEA provides detailed guidelines: http://hiv.net/link.php?id=120. A rash, often pruritic and usually occurring within the first six weeks of treatment, can be treated with antihistamines if mucous membranes are not involved and if transaminases are normal. Topical formulations are effective against pruritus. Nevirapine must be discontinued if a severe rash occurs; in these cases, steroids may be used (eg. prednisolone 1 mg/kg for 3-5 days). Nevirapine should also be discontinued if other systemic symptoms occur (fever, conjunctivitis, myalgia, arthralgia, malaise). If the rash occurs during the first two weeks of treatment, the dose should not be increased until the rash has resolvedcompletely. Prophylactic treatment with steroids is not advised(Kamps and Hoffman, 2003).
- Drug Resistance: As with all NNRTIs, a single point mutation is sufficient to develop a highlevel resistance(Kamps and Hoffman, 2003).
- Ritonavir (RTV) [Trade name: Norvir] (Kamps and Hoffman, 2003): Due to its gastrointestinal side effects, the therapeutic dose ofritonavir is hardly acceptable and rarely prescribed. However, ritonavir has become an important drug for boosting other protease inhibitors. In these combinations, when lower doses are used, side effects of ritonavir are tolerable. Numerous drug interactions must be considered. FORMULATIONS: 100 mg capsules, 80 mg/ml oral solution, 240 ml DOSE: In rare cases, in which ritonavir is used as a single PI, the dose is 600 mg bid (increase dose over two weeks: 300 mg bid on day 1-2, 400 mg bid on day 3-5, 500 mg bid on day6-13). BOOSTING: The optimal use of ritonavir, however, is for boosting of other PIs! Daily doses in combination with Saquinavir (Fortovase or Invirase) - 100 mg ritonavir bid + 1000 mg saquinavir bid or 400 mg ritonavir bid + 400 mg saquinavir bid; Indinavir (Crixivan) - 100 mg ritonavir bid + 800 mg indinavir bid or 400 mg ritonavir bid + 400 mg indinavir bid; Amprenavir (Agenerase) - 100 mg ritonavir bid + 600 mg amprenavir bid or 200 mg ritonavir qd + 1200 mg amprenavir qd; Lopinavir (Kaletra) - Fixed combination, see lopinavir(Kamps and Hoffman, 2003).
- Contraindicator: Even the low boosting doses used incombination with other PIs have multiple drug interactions! The following are contraindicated: rifampicin, amiodarone, astemizole, bepiridil, terfenadine, encainide, flecainide, cisapride, triazolam, ergotamine, simvastatin, lovastatin, quinidine, and St. Johns wort. Sildenafil should be avoided! Caution should be taken and plasma levels measured for both ritonavir and (if possible) the following co-medications: Methadone,immunosuppressants (cyclosporine, tacrolimus), macrolide antibiotics (erythromycin, clarithromycin), steroids, calcium antagonists, tricyclic antidepressants, other antidepressants (fluoxetine, paroxetine, sertraline), neuroleptics (haloperidol, risperidone, thioridazine), antimycotic drugs (ketoconazole, itraconazole), carbamazepine, tolbutamide, rifabutin, theophylline, and warfarin(Kamps and Hoffman, 2003).
- Complication: Very frequent with therapeutic doses: nausea,vomiting, diarrhea, headache, perioral paresthesia and electric sensations on arms and legs. Elevated transaminases and gammaGT, often significant dyslipidemia, reduced glucose tolerance and, rarely, diabetes mellitus. Lipodystrophy with long-term treatment(Kamps and Hoffman, 2003).
- Saquinavir (SQV) [Trade name: Fortovase, Invirase] (Kamps and Hoffman, 2003): One of the first PIs, and the only one with two available formulations.Relatively "benign" (well tolerated except for gastrointestinal problems, no serious short-term problems). Intolerable pill burden if unboosted. Due to low bioavailability, the formulation was improved from Invirase to Fortovase, which is unfortunately less well tolerated. According to recent data, Invirase, which had almost been abandoned, is just as effective when boosted with ritonavir. Strangely enough, Invirase issignificantly more expensive. Cross-resistance with other PIs is frequent. FORMULATIONS: 200 mg capsules (Invirase) 200 mg soft gel capsules (Fortovase) DOSE: Treatment without boosting (only in exceptions): 1200 mg tid (6 capsules tid). Combination with ritonavir is generally preferred: Fortovase or Invirase: 1000 mg bid plus 100 mg ritonavir bid is optimal. An alternative is 400 mg ritonavir bid plus 400 mg Fortovase or Invirase(Kamps and Hoffman, 2003).
- Contraindicator: Contraindicated for concurrent treatment with rifampicin, astemizole, terfenadine, cisapride, triazolam, ergotamine, simvastatin, lovastatin, and St. Johns wort. If saquinavir is not combined with other protease inhibitors it must be taken with meals(Kamps and Hoffman, 2003).
- Complication: Mainly gastrointestinal: diarrhea, nausea, abdominal discomfort, meteorism. Rarely elevation of transaminases or GT, headache. As with other PIs, lipodystrophy, dyslipidemia and reduced glucose tolerance may occur with long-term treatment(Kamps and Hoffman, 2003).
- Stavudine (d4T) [Trade name: Zerit] (Kamps and Hoffman, 2003): Stavudine is a thymidine analog like zidovudine. Subjective tolerability is good; the drug was long considered at least equivalent to zidovudine. Newer guidelines are more cautious, due to neuropathy and data on mitochondrial toxicity (lipoatrophy, lactic acidosis), particularly in combination with didanosine. New 75 mg and 100 mg capsules will be available shortly, allowing once-daily dosing. FORMULATIONS: Capsules: 15 mg, 20 mg, 30 mg, 40 mg 1 mg/ml oral solution, 200 ml Extended-Release Capsules, 37.5 mg, 50 mg, 75 mg, and 100 mg DOSE: 40 mg bid (body weight > 60 kg), or 30 mg bid (body weight < 60 kg)(Kamps and Hoffman, 2003).
- Contraindicator: Stavudine should not be combined withzidovudine due to antagonistic effects. If possible, no concurrent treatment with other neurotoxic drugs (zalcitabine, ethambutol, cisplatin, INH, vincristine, etc.) Stavudine can be taken on an empty stomach or with a light meal. If symptoms of peripheral neuropathy occur, treatment with stavudine should be discontinued(Kamps and Hoffman, 2003).
- Complication: Peripheral neuropathy, especially in combination with didanosine (up to 24 %). In many studies, stavudine has been linked to lipoatrophy more than other NRTIs. However,the following are less frequent than with zidovudine: diarrhea, nausea, vomiting, headache. Very rare, but potentially fatal: lactic acidosis which occurs mostly in combination with didanosine (especially in pregnancy!). Further side effects: hepatic steatosis, pancreatitis(Kamps and Hoffman, 2003).
- T-20 (Enfuvirtide) [Trade name: Fuzeon] (Kamps and Hoffman, 2003): T-20 is the prototype of a new drug class the entry inhibitors.It is well tolerated, but can only be administered as an injection. It will be important for salvage therapy in the future. FORMULATIONS: Vials, 90 mg; supplied as 30-day kit with tools required for self-injection. The powder is reconstituted with sterile water prior to subcutaneous injection. DOSE: 90 mg subcutaneously bid. In pediatric patients six years through 16 years of age, a dose of 2 mg per kg of body weight (maximum 90 mg) administered twice-daily, provided plasma concentrations similar to those obtained in adult patients receiving 90 mg, twice-daily(Kamps and Hoffman, 2003).
- Complication: Generally well tolerated. Local injection site reactions are the most frequent adverse events associated with the use of T-20. In Phase III clinical studies, 98 percent of patients had at least one local reaction at the injection site. Manifestations of injection site reactions may include pain and discomfort, induration, erthyema, nodules and cysts, prurities, and ecchymosis (change injection site). Hypersensitivity reactions have been associated with T-20(<1 %) and have recurred on rechallenge. Symptoms of an allergic reaction may include rash, fever, nausea and vomiting, chills, rigors, hypotension, and elevated serum transaminases(Kamps and Hoffman, 2003).
- Tenofovir (TDF) [Trade name: Viread] (Kamps and Hoffman, 2003): Tenofovir DF is the prodrug of the acyclic nucleotide analog tenofovir, and has good oral bioavailability. It also has efficacy against hepatitis B virus. Tenofovir, at least according to current data, has good tolerability. FORMULATIONS: 300 mg tablets DOSE: 300 mg qd, to be taken with a meal(Kamps and Hoffman, 2003).
- Contraindicator: Tenofovir should not be prescribed topatients with a creatinine clearance of less than 60 ml/min. In cases of mild renal dysfunction, retention parameters should be monitored monthly. Concurrent treatment of tenofovir and other drugs that are eliminated via active tubular secretion can lead to increased serum concentrations of both drugs: cidofovir, aciclovir, valaciclovir, ganciclovir, valganciclovir. Use with caution in combination with didanosine: comedication with tenofovir increases the Cmax and AUC of didanosine by 28 % and 44 %, respectively. Even though the data published so far does not show an increased incidence in the side effects typical of didanosine, the dose of didanosine should be reduced to 250 mg. Tenofovir should be taken two hours before or one hour after didanosine. Controlled studies on the use of tenofovir in pregnancy are yetto come. In monkey studies, tenofovir was effective in the prophylaxis of SIV transmission, but also resulted in growth disorders(Kamps and Hoffman, 2003).
- Complication: Generally well tolerated. In several studies, side effects were comparable to those reported in placebos. Rarely: elevation of liver enzymes; possibly leucopenia. It is not currently known, whether long-term treatment with tenofovir can lead to bone density changes. Animal studies showed changes in bone density at doses 30 times higher than the therapeutic dose. In contrast to its predecessor, adefovir, there has been no indication of nephrotoxicity however, there is no long-term data available yet(Kamps and Hoffman, 2003).
- Tipranavir (Kamps and Hoffman, 2003): Tipranavir is the first non-peptide PI and shows good efficacyagainst PI-resistant viruses. It has low oral bioavailability and therefore requires boosting with ritonavir. Tipranavir is still under clinical investigation. DOSE: Tipranavir is being tested in Phase III studies at a dose of 500 mg bid plus 200 mg ritonavir bid(Kamps and Hoffman, 2003).
- Contraindicator: Co-medication with rifampicin and delavirdine is contraindicated. Antacids reduce tipranavir levels by 30 %(Kamps and Hoffman, 2003).
- Complication: Diarrhea, vomiting, headache, abdominal pain.Rarely: dizziness, fatigue, elevated transaminases(Kamps and Hoffman, 2003).
- Trizivir (Kamps and Hoffman, 2003): This combination has led to a significant reduction in the pillburden. It is the simplest triple combination currently available. See also the individual drugs zidovudine, lamivudine and abacavir. FORMULATIONS: Tablets containing 150 mg lamivudine and 300 mg zidovudine and 300 mg abacavir. DOSE: 1 tablet bid. In cases of impaired renal function (creatinine clearance less than 50 ml/min), the individual drugs should be given separately to allow the doses of lamivudine and zidovudine to be adjusted(Kamps and Hoffman, 2003).
- Contraindicator: Watch closely for hypersensitivity reactions(see abacavir). See individual drugs(Kamps and Hoffman, 2003).
- Complication: Mostly gastrointestinal, see the individual drugs. Hypersensitivity reaction with abacavir (see under abacavir!). There are possible additive effects with regard to mitochondrialtoxicity(Kamps and Hoffman, 2003).
- Zalcitabine (ddC) [Trade name: Hivid] (Kamps and Hoffman, 2003): One of the first antiretroviral drugs. It is now used very rarelydue to complicated dosing, risk of polyneuropathy and crossresistance with didanosine. It is possibly less potent than didanosine and stavudine. FORMULATIONS: 0.375 mg tablets, 0.75 mg tablets DOSE: 0.75 mg tid. Dose adjustment for renal failure: Creatinineclearance of 40 to 10 ml/min: 0.75 mg bid, CrCl <10 ml/min: 0.75 mg qd(Kamps and Hoffman, 2003).
- Contraindicator: Zalcitabine is contraindicated in patientswith pre-existing polyneuropathy. Use with caution with history of pancreatitis. Zalcitabine should not be administered with neurotoxic drugs,e.g. ethambutol, cisplatin, disulfiram, ethionamide, INH, vincristine. Combination of didanosine and stavudine is not recommended, as there is little available data and risk of crossresistance. Combination with zidovudine is best(Kamps and Hoffman, 2003).
- Complication: Peripheral neuropathy (up to 30 %), stomatitiswith oral ulcers (up to 4 %), pancreatitis (<1 %). Rarely rash, lactic acidosis, hepatic steatosis(Kamps and Hoffman, 2003).
- Zidovudine (AZT) [Trade name: Retrovir, Combivir, Trizivir] (Kamps and Hoffman, 2003): The oldest and best investigated HIV drug. Due to gastrointestinaland myelotoxic side effects, the drug was out of fashion for a while. However, it remains an important component of many HAART regimens even today, particularly as it has good CNS penetration and relatively low mitochondrial toxicity (good long-term tolerability!). FORMULATIONS: Retrovir - 100 mg capsules; 250 mg capsules; 300 mg tablets; 10 mg/ml syrup, 240 ml; 20 ml intravenous vials, 10 mg/ml; Combivir - Tablets containing 300 mg zidovudine and 150 mg lamivudine; Trizivir - Tablets containing 300 mg zidovudine and 150 mg lamivudine and 300 mg abacavir DOSE: 250 mg bid or 200 mg tid. In Combivir and Trizivir 300 mg bid. Creatinine clearance below 20 ml/min: 300 bis 400 mg daily. Hemodialysis: 300 mg daily. Hepatic failure: 100 mg tid(Kamps and Hoffman, 2003).
- Contraindicator: Do not combine with stavudine! Thereis increased myelotoxicity with concurrent use of other myelosuppressive drugs, especially ganciclovir, but also cotrimoxazole, dapsone, etoposide, pyrimethamine, interferon, daunorubicin, vinblastine, vincristine, sulfadiazine, amphotericin B and ribavirin. Ribavirin antagonizes the antiviral activity of zidovudine in vitro. Concurrent use of zidovudine and ribavirin should therefore be avoided. Initially monthly monitoring of blood count, transaminases, CPK and bilirubin. The gastrointestinal complaints can be treated symptomatically and usually subside after a few weeks. Anemia can develop even after months. Zidovudine should always be a component of transmission prophylaxis!(Kamps and Hoffman, 2003).
- Complication: Nausea, vomiting, abdominal discomfort, headache, myalgia, dizziness. Macrocytic anemia (MCV almost always elevated), rarely neutropenia. Elevations in LDH, CPK and transaminases may occur. Episodes of lactic acidosis are rare(Kamps and Hoffman, 2003).
- Post Exposure Prophylaxis (CDC, 1998): Decisions to provide antiretroviral agents to persons after possible nonoccupational HIV exposure to prevent the establishment of HIV infection must balance the potential benefits and risks. Factors influencing the potential efficacy of this intervention include the probability that the source contact is HIV-infected, the likelihood of transmission by the particular exposure, the interval between exposure and initiation of therapy, the efficacy of the drug(s) used to prevent infection, and the patients adherence to the drug(s) prescribed. The major potential benefit of antiretroviral postexposure prophylaxis is reducing a persons risk for acquiring HIV infection after exposure. Potential risks of antiretroviral postexposure prophylaxis include drug toxicity, reduced effectiveness of behavioral HIV-prevention measures, and the acquisition of antiretroviral-resistant HIV strains. Also, the cost of medications could tax already scarce public funds for antiretroviral agents for HIV-infected persons, which offer costeffectiveness and therapeutic benefit(CDC, 1998). This guideline recommends aggressive initiation of antiretroviral therapy promptly after a high-risk injury; if there is any question about the indication for antiretroviral therapy, then expert consultation should be obtained. If expert advice is not available then the therapy should be initiated and reevaluated after a few days. The Centre provides a starter kit of 5 days therapy of Stavudine (d4T), and Lamivudine (3TC) and Nelfinavir which is now the standard of care for significant exposures. DOSES: Stavudine - one capsule (40 mg) twice a day for four weeks; Lamivudine (3TC) - one tablet (150 mg) twice a day for four weeks; Nelfinavir - five tablets (1250 mg) twice a day with meals for four weeks. Take all three drugs with food. The remainder of the one-month's therapy will be supplied by the Centre by calling the Centre Pharmacy at. Therefore, follow-up of the exposed person by their physician within the first few days of therapy is essential. The starter kit is intended to provide 5 days of therapy while a more detailed assessment of the risk of transmission can occur. The exposed person should see their family physician or designated follow-up physician as soon as possible after the initiation of the starter kit to determine the need for a full 28 days of therapy. Many exposed persons will not require 28 days of therapy, but this decision should be made in consultation with their physician. If 28 days of therapy are necessary, the physician should contact the Centre Pharmacy as soon as possible to expedite securing the remaining 23 days of therapy(The Therapeutic Guidelines for the Treatment of HIV/AIDS and Related Conditions).
- Contraindicator: There are many drug interactions with antiretroviral therapy, particularly with protease inhibitors. A careful medication history and use of all alternate therapy should be reviewed. Non-essential medications and all alternate therapy should be discontinued during antiretroviral therapy, questions regarding drug interactions should be directed to the Centre Pharmacy. Avoid or use with extreme caution in persons with chronic renal insufficiency (creatinine more than three times normal), hepatic insufficiency, or bone marrow dyscrasia. Avoid or use with extreme caution in persons treated with myelosuppressive, nephrotoxic or hepatotoxic drugs in the two weeks prior to starting antiretroviral therapy. If the exposed person is pregnant, contact the Centre Pharmacy as soon as possible. It should be explained to the exposed person these drugs have been used extensively in pregnant women and well tolerated. If there has been a significant exposure, prophylaxis should be started(The Therapeutic Guidelines for the Treatment of HIV/AIDS and Related Conditions).
- Complication: These estimates are based on the experience of the Centre for Excellence in the use of HIV prophylaxis and also use in the treatment of HIV infection. In most cases, the estimates are based on the use of two drugs and the adverse effects of three drugs may be higher. Minor adverse reactions e.g. nausea, fatigue, etc. (70% of patients). Serious reactions e.g. unable to work for the month of therapy (30 - 60% of patients) Long term adverse effects (poorly defined) 1:5,000. Risk of death is unknown but we would estimate that the risk of dying is 1:15,000 to 1:150,000. With three drugs without good follow-up such as accidental exposures, it may actually be much higher(The Therapeutic Guidelines for the Treatment of HIV/AIDS and Related Conditions).
- Hydroxyurea (Kelly et al., 2004): Hydroxyurea has been in use for more than forty years in hematology, originally for the treatment of myeloproliferative disorders, and has recently been approved for the treatment of sickle-cell anemia. Hydroxyurea directly inhibits the cellular enzyme ribonucleotide reductase, thereby blocking the transformation of ribonucleotides into deoxynucleotides, depleting the intracellular deoxynucleotide triphosphate (dNTP) pool and arresting the cell cycle in the G1/S phase. Hydroxyurea exerts direct antiviral effects by inhibiting viral replication in macrophages, which mediate neuronal damage during HIV infection, at much lower concentrations than those required in activated T lymphocytes, possibly because macrophages are terminally differentiated cells with low constitutive dNTP levels. Hydroxyurea also exerts indirect antiviral effects, by offering a selective advantage to nucleoside analogues by decreasing cellular dNTPs. dATP analogues, such as ddI, will synergize best with hydroxyurea because of their unusual susceptibility of dATP pools to depletion by hydroxyurea relative to other dNTPs (as mentioned above). Another proposed indirect mechanism of viral inhibition by hydroxyurea is the enhancement of enzyme kinetics in the conversion of NRTI pro-drugs to active metabolites. Besides the antiviral effects, hydroxyurea might inhibit HIV replication through an immunomodulating, cytostatic effect, by preventing T cell proliferation, thus reducing HIV cellular targets. This mechanism might also be common to the other cytostatic drugs reviewed here, such as MPA and LF. It is very important to realize that these cytostatic effects might provide additional benefits during chronic HIV infection by cooling down an over-heated immune system. DOSE: optimal daily dose of 600 mg hydroxyurea(Kelly et al., 2004).
- Contraindicator: It is also important to stress that hydroxyurea is teratogenic and therefore should not be prescribed during pregnancy or to lactating mothers(Kelly et al., 2004).
- Complication: Hydroxyurea when prescribed alone has been associated with mild gastrointestinal complaints such as nausea, vomiting, diarrhea and anorexia; however, these symptoms rarely require cessation of therapy. The prolonged use of hydroxyurea infrequently causes skin toxicities such as alopecia, hyperpigmentation, erythma and leg ulcers. In addition, transient abnormalities in renal and hepatic function have been reported. The most severe side effects include neutropenia, anemia and thrombocytopenia all of which are dose related and more probable when hydroxyurea is combined with other bone marrow suppressing agents such as AZT(Kelly et al., 2004).
- Drug Resistance: Since this virostatic combination is characterized by an excellent resistance profile and potent antiretroviral activity it could prove to be a valuable therapeutic option for the long-term management of HIV/AIDS worldwide(Kelly et al., 2004).
- Mycophenolic acid (MPA) [Trade name: CellCept] (Kelly et al., 2004): Mycophenolate mofetil (CellCeptTM), the pro-drug of mycophenolic acid, (for simplicity we will only use mycophenolic acid, MPA) is licensed for the prevention of renal transplant rejection and has been extensively investigated in different models of allogeneic transplantation, autoimmune skin disorders and rheumatoid arthritis. In order to assess the advantages of adding MPA to HIV regimens in patients failing therapy, two pilot studies have been conducted. At 250 mg BID MPA appears safe, but virologic responses were transient. A second study was initiated with a higher dosage of MPA. Subjects added MPA (500 mg BID) to drug regimens known to synergize with MPA. Viral load decreased > 0.5 log10 copies/ml in 3 of 5 subjects after 24 weeks and 2 of 5 patients maintained this decrease up to their last study visit at week 64(Kelly et al., 2004).
- Complication: The principal adverse reactions associated with the administration of MPA include diarrhea, leukopenia, sepsis and vomiting, and there is evidence of a higher frequency of certain types of infections(Kelly et al., 2004).
- Prevention:
- Antiretroviral drugs to prevent transmission through breast-feeding(Gaillard et al., 2002)
- Description: Findings from several trials in breast-feeding settings support the efficacy of ultrashort (intrapartum and 1 week postpartum) courses of infant antiretroviral prophylaxis using 3 different regimens (NVP, ZDV alone, ZDV/3TC) in reducing the risk of MTCT. However, these peripartum interventions do not address prevention of late breast-feeding transmission after the first weeks of life(Gaillard et al., 2002),
- Efficacy:
- Male circumcision
- Description: Male circumcision consistently shows a protective effect against HIV infection. This may be due to the abundance of Langerhans cells in the foreskin or to a receptive environment for HIV in the sulcus between the foreskin and glans. The prevalence of HIV infection is 1.7 to 8.2 times as high in men with foreskins as in circumcised men, and the incidence of infection is 8 times as high. A greater proportion of the sex partners of uncircumcised men than of circumcised men are infected with HIV, which suggests that the presence of the foreskin may also increase infectiousness(Royce et al., 1997), Circumcised men have a reduced risk of HIV-1 infection compared with uncircumcised men. Some investigators have argued that circumcision is simply an epidemiological marker of reduced behaviours related to risk of HIV-1 infection, including religious or cultural factors. Others have suggested that circumcision reduces the risk of other sexually transmitted diseases associated with genital ulceration or mucosal inflammation, which secondarily reduces the risk of HIV-1. After adjusting for sociodemographic and behavioural risk factors in the proportional hazards model, circumcision had no significant protective effect on incident HSV-2, syphilis, or gonococcal urethritis. Circumcision was strongly protective against HIV-1 acquisition, with a 67-fold reduction in risk of HIV-1 infection among circumcised men. A unique and important finding from this study was a highly significant and specific protective effect of male circumcision on the risk of HIV-1 acquisition. Our data failed to show a significant protective effect of circumcision on the risk of the other STIs. These epidemiological data lend support to the hypothesis that male circumcision protects against HIV-1 infection primarily due to removal of the foreskin, which contains a high density of HIV-1-specific cellular targets, including CD4+ T-lymphocytes and Langerhans cells, which are easily accessible to the virus through the thin layer of keratin overlying the inner mucosa(Reynolds et al., 2004), The exhaustive Cochrane review of the evidence for possible protection from female-to-male sexual transmission of HIV-1 by circumcision concluded that insufficient evidence exists to support an interventional effect of male circumcision inheterosexual males(Boyle, 2004),
- Efficacy:
- Complication: CULTURAL ACCEPTANCE: Circumcision would not be culturally acceptable to Hindu men. In addition, there are other factors to consider before taking any decision to introduce circumcision. These include potential adverse medical and psychosexual effects, as well as legal, ethical, and human rights issues(Boyle, 2004),
- Expanded Screening
- Description: Although the Centers for Disease Control and Prevention (CDC) recommend routine HIV counseling, testing, and referral (HIVCTR) in settings with at least a 1 percent prevalence of HIV, roughly 280,000 Americans are unaware of their human immunodeficiency virus (HIV) infection. In the high-risk population, the addition of one-time screening for HIV antibodies with an enzyme-linked immunosorbent assay (ELISA) to current practice was associated with earlier diagnosis of HIV (mean CD4 cell count at diagnosis, 210 vs. 154 per cubic millimeter). One-time screening also improved average survival time among HIVinfected patients (quality-adjusted survival, 220.7 months vs. 219.8 months). The incremental cost-effectiveness was $36,000 per quality-adjusted life-year gained. Testing every five years cost $50,000 per quality-adjusted life-year gained, and testing every three years cost $63,000 per quality-adjusted life-year gained. In the CDC threshold population, the cost-effectiveness ratio for one-time screening with ELISA was $38,000 per quality-adjusted life-year gained, whereas testing every five years cost $71,000 per quality-adjusted life-year gained, and testing every three years cost $85,000 per qualityadjusted life-year gained. In the U.S. general population, one-time screening cost $113,000 per quality-adjusted life-year gained. Under current screening practices in the high-risk population, we expect to observe 44,000 to 60,000 secondary transmissions per 100,000 participants in the screening program. A single ELISA could avert up to 300 of these secondary transmissions. Repeated testing every five years, three years, and one year could avert 2700, 3600, and 5100 infections, respectively. In all but the lowest-risk populations, routine, voluntary screening for HIV once every three to five years is justified on both clinical and cost-effectiveness grounds. One-time screening in the general population may also be cost-effective(Paltiel et al., 2005),
- Model System:
- Chimpanzees (Pan troglodytes)(Joag, 2000)
- Model Host: Animals (non-human).
HIV-1 can readily be transmitted to common chimpanzees(Joag, 2000),
- Model Pathogens:
- Description: In the light of recent confirmation that SIVcpz is the progenitor of HIV-1, it is not surprising that HIV-1 can readily be transmitted to common chimpanzees (Pan troglodytes). The great advantages of the HIV-1/chimpanzee model are the close phylogenetic relationship between chimpanzees and humans and the fact that the virus strains used are derived from patients, so results obtained using this model are likely to be highly relevant to AIDS in humans. Despite the advantage of working with HIV-1, there are important drawbacks associated with the HIV-1/chimpanzee model. Chimpanzees are rare, endangered, and expensive; precluding their use in experiments that require large numbers of animals. Government regulations, ethical considerations, and opposition from animal rights advocates are other factors that restrict wide use of this model(Joag, 2000),
- SIVmac of HIV-2 in Macaque monkeys (Macaca sp.)(Joag, 2000)
- Model Host: Animals (non-human).
SIVmac infection in macaque monkeys is a well-characterized model of AIDS(Joag, 2000),
- Model Pathogens:
HIV-2 and SIVsmm infections of macaques resemble SIVmac infections in most respects and in this review are considered as lying within the framework of the SIVmac/macaque model(Joag, 2000).
- Description: The SIVmac model has been used extensively for studies on pathogenesis and virus-host cell interactions, despite the biological differences between HIV-1 and SIVmac/HIV-2/SIVsmm. Recent studies that have exploited this model include the demonstration that repeated stimulation of the immune system by BCG inoculation in an SIV-infected macaque led to sequential waves of virus replication and data showing that disease progression in infected macaques was dependent on viral RNA levels of more than 100 000 RNA equivalents/mL of plasma. The SIVmac/macaque model has proven useful in defining the mechanisms of pathogenesis for organspecific disease, such as encephalitis. The SIVmac/macaque model is also useful for studies of transmission, as exemplified by Sodora et al., who showed that macaques are resistant to infection when exposed to infected cells by the vaginal route, although cell-free virus was able to infect animals by this route, particularly during the luteal phase of the menstrual cycle. In another example of the utility of the SIVmac /macaque model in transmission studies, Amedee et al. provided evidence for genotypic and phenotypic selection in transplacental transmission of SIV. Immune responses in infected macaques parallel those in humans. In both cases, cell-mediated immune responses suppress virus replication while the appearance of neutralizing antibodies does not inhibit virus replication. The principal neutralizing domains of SIVmac appear to be conformational, rather than linear as in the case of HIV-1. This limits the usefulness of the SIVmac model for evaluating passive immunization and HIV-1 envelope vaccine approaches. Except for the non-nucleoside reverse transcriptase inhibitors, most antiretrovirus drugs have similar efficacy against HIV-1 and SIVmac, allowing the SIVmac/macaque model to be used in studying effectiveness of antiviral drugs in vivo(Joag, 2000),
- SIVmac of HIV-2 in Baboons (Papio sp.)(Joag, 2000)
- Model Host: Animals (non-human).
Although macaques have been predominantly used in models based on viruses of the SIVsmm/HIV-2/SIVmac group, these viruses can also infect baboons (Papio cynocephalus)(Joag, 2000),
- Model Pathogens:
Although macaques have been predominantly used in models based on viruses of the SIVsmm/HIV-2/SIVmac group, these viruses can also infect baboons (Papio cynocephalus)(Joag, 2000).
- Description: Although macaques have been predominantly used in models based on viruses of the SIVsmm/HIV-2/SIVmac group, these viruses can also infect baboons (Papio cynocephalus) and models have been developed using this species. However, infection appears to not be pathogenic in a majority of cases, though some virulent strains have been described. Even when a pathogenic virus strain is used, the baboon model does not appear to have any significant advantages over the macaque model when using viruses of the SIVmac/HIV-2/SIVsmm group(Joag, 2000),
- Transgenic Mouse (Mus musculus) with human CD4
- Model Host: Animals (non-human).
We have generated transgenic mice predominantly expressing human CD4 and CXCR4 on their CD4-positive T lymphocytes (CD4+ T cells)(Sawada et al., 1998),
- Model Pathogens:
Their primary thymocytes are susceptible to T-tropic but not to macrophage-tropic HIV-1 infection in vitro, albeit with a viral antigen production less efficient than human peripheral blood mononuclear cells(Sawada et al., 1998).
- Description: T cell line-tropic (T-tropic) HIV type 1 strains enter cells by interacting with the cell-surface molecules CD4 and CXCR4. We have generated transgenic mice predominantly expressing human CD4 and CXCR4 on their CD4-positive T lymphocytes (CD4+ T cells). Their primary thymocytes are susceptible to T-tropic but not to macrophage-tropic HIV-1 infection in vitro, albeit with a viral antigen production less efficient than human peripheral blood mononuclear cells. Interestingly, even without HIV infection, transgenic mice display a CD4+ T cell depletion profile of peripheral blood reminiscent of that seen in AIDS patients. We demonstrate that CD4+ T cell trafficking in transgenic mice is biased toward bone marrow essentially due to CXCR4 overexpression, resulting in the severe loss of CD4+ T cells from circulating blood. Our data suggest that CXCR4 plays an important role in lymphocyte trafficking through tissues, especially between peripheral blood and bone marrow, participating in the regulation of lymphocyte homeostasis in these compartments. Based on these findings, we propose a hypothetical model in which the dual function of CXCR4 in HIV-1 infection and in lymphocyte trafficking may cooperatively induce progressive HIV-1 infection and CD4+ T cell decline in patients(Sawada et al., 1998),
- Transgenic Mouse (Mus musculus) with integrated HIV-1(Hanna et al., 1998)
- Model Host: Animals (non-human).
We have constructed transgenic (Tg) mice expressing the entire human immunodeficiency virus type 1 (HIV-1) coding sequences in cells targeted by HIV-1 infection in humans. These Tg mice developed a severe AIDS-like disease leading to early death (<1 month)(Hanna et al., 1998),
- Model Pathogens:
Expression of HIV-1 with this promoter should mimic more closely the expression of HIV-1 detected in HIV-1-infected individuals(Hanna et al., 1998).
- Description: Our results show that Tg mice expressing the complete HIV-1 coding sequences under the regulation of the CD4C promoter develop a severe AIDS-like disease followed by early death. We have previously reported that this promoter, derived from the human and mouse CD4 genes, allows expression of surrogate genes in CD41 CD81 and CD41 thymocytes, in peripheral CD41 T cells, and in macrophages. Expression of the transgene in CD4C/HIVWT mice was found to be apparently in the same cells, namely, T cells and macrophages. In addition, we have recently documented by further examination of CD4C/CD4 Tg mice that this promoter is active in spleen dendritic cells. These represent the specific subsets of cells which are normally targeted for infection by HIV-1 in humans. Expression of HIV-1 in these specific cell populations of Tg mice appears to be important to elicit this AIDS-like disease, since our other mice similarly expressing the whole HIV-1 genome at high levels in different cell populations and through different promoters did not develop any apparent abnormal phenotype of the immune system(Hanna et al., 1998),
- SCID mice (Mus musculus) with human xenograft(Rabin et al., 1996)
- Model Host: Animals (non-human).
We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for the prophylactic administration of antiviral compounds and for evaluation of the antiviral effect in vivo(Rabin et al., 1996),
- Model Pathogens:
- Description: We have now developed a SCID-hu model using conjoint implants of human fetal thymus and liver (to create SCID-hu Thy/Liv mice). These implants have been shown previously to be vascularized and to grow when implanted beneath the kidney capsule, eventually reaching a total mass of 10 to 100 million human cells. Such growth occurs in 80 to 90% of recipients and is relatively unaffected by variable parameters in the SCID mouse colony. For periods of time as long as 12 months in vivo, the Thy/Liv organs sustain multilineage human hematopoiesis and provide for a continuous source of normal human CD4+ T cells. By using the current model, single antiviral agents can be tested in a dose-ranging manner against four standardized virus stocks, including two molecularly cloned viruses and two primary isolates. The effects of such agents on the course of HIV-1 replication can then be assessed with PCR-based detection of viral DNA, p24 enzyme-linked immunosorbent assay (ELISA) for viral replication, flow cytometry for T-cell subpopulations, and semiquantitative assays for virus isolation. Given the data that can be obtained about the effects of various antiviral compounds in vivo, this SCID-hu model may provide a useful means for the evaluation of preclinical lead compounds prior to movement into the clinic(Rabin et al., 1996),
- Transgenic Rat (Rattus sp.) with human CD4(Keppler et al., 2002)
- Model Host: Animals (non-human).
In vivo, hCD4/hCCR5 transgenic rats challenged systemically with HIV-1 showed clear evidence of successful infection(Keppler et al., 2002),
- Model Pathogens:
- Description: Here we report the generation of transgenic rats that coexpress hCD4 and hCCR5 on CD4+ T lymphocytes, macrophages, and microglia. Coexpression of these human transgenes rendered primary rat cells permissive for infection by R5 viruses. In ex vivo cultures, cells of the monocyte/macrophage lineage from these animals could be productively infected by various R5 viruses at levels one to two orders of magnitude higher than those described for comparable transgenic mouse models. In vivo, hCD4/hCCR5 transgenic rats challenged systemically with HIV-1 showed clear evidence of successful infection demonstrated by detection of episomal and integrated HIV-1 cDNA, and early gene expression in cells from spleen, thymus, and blood. Low-level plasma viremia was detectable in transgenic rats up to 7 wk after inoculation. These important steps provide a strong foundation for studies that will address the extent of HIV-1 replication, pathogenesis, and immune responses to HIV-1 in transgenic rats in vivo and elucidate their potential for testing of antiviral strategies(Keppler et al., 2002),
- Transgenic Rat with integrated HIV-1(Reid et al., 2001)
- Model Host: Animals (non-human).
The first HIV type 1 (HIV-1) transgenic (Tg) rat(Reid et al., 2001),
- Model Pathogens:
- Description: We report, to our knowledge, the first HIV type 1 (HIV-1) transgenic (Tg) rat. Expression of the transgene, consisting of an HIV-1 provirus with a functional deletion of gag and pol, is regulated by the viral long terminal repeat. Spliced and unspliced viral transcripts were expressed in lymph nodes, thymus, liver, kidney, and spleen, suggesting that Tat and Rev are functional. Viral proteins were identified in spleen tissue sections by immunohistochemistry and gp120 was present in splenic macrophages, T and B cells, and in serum. Clinical signs included wasting, mild to severe skin lesions, opaque cataracts, neurological signs, and respiratory difficulty. Histopathology included a selective loss of splenocytes within the periarterial lymphoid sheath, increased apoptosis of endothelial cells and splenocytes, follicular hyperplasia of the spleen, lymphocyte depletion of mesenteric lymph nodes, interstitial pneumonia, psoriatic skin lesions, and neurological, cardiac, and renal pathologies. Immunologically, delayed-type hypersensitivity response to keyhole limpet hemocyanin was diminished. By contrast, Ab titers and proliferative response to recall antigen (keyhole limpet hemocyanin) were normal. The HIV-1 Tg rat thus has many similarities to humans infected with HIV-1 in expression of viral genes, immune-response alterations, and pathologies resulting from infection. The HIV-1 Tg rat may provide a valuable model for some of the pathogenic manifestations of chronic HIV-1 diseases and could be useful in testing therapeutic regimens targeted to stages of viral replication subsequent to proviral integration(Reid et al., 2001),
- Transgenic Rabbit (Leporidae sp.) with human CD4(Dunn et al., 1995)
- Model Host: Animals (non-human).
The laboratory rabbit has been described as being susceptible to HIV-1 infection but very large doses of virus were used for inoculation, virus was difficult to detect and these initial results have not been successfully repeated in other studies. These shortcomings render the normal laboratory rabbit a poor animal model of HIV infection(Dunn et al., 1995),
- Model Pathogens:
- Description: The laboratory rabbit has been described as being susceptible to HIV-1 infection but very large doses of virus were used for inoculation, virus was difficult to detect and these initial results have not been successfully repeated in other studies. These shortcomings render the normal laboratory rabbit a poor animal model of HIV infection but it has been shown that the susceptibility of rabbit cell lines to infection could be enhanced by expression of the human CD4 gene. The role of the CD4 protein as the principal receptor for the primate lentiviruses is a well-documented aspect of their replication cycle and so transgenic rabbits specifically expressing the human CD4 (huCD4) molecule on T lymphocytes may represent a significant advance in the development of a new animal model of HIV-1 infection. In vivo infection of huCD4-transgenic rabbits using HIV-1(IIIB)-infected autologous lymphocytes was demonstrated by virus isolation, detection of HIV-1-specific DNBA in peripheral blood lymphocytes and seroconversion to various HIV-1 proteins. Viral DNA was detected in the tissues of one rabbit sacrificed 7 weeks post-infection and virus was isolated from lymph node. Although these transgenic rabbits are less sensitive to HIV-1 infection than man, such a small and inexpensive animal model may be a useful tool(Dunn et al., 1995),
- Transgenic Fly (Drosophila melanogaster) with HIV-1 tat gene(Battaglia et al., 2001)
- Model Host: Animals (non-human).
We produced a Drosophila melanogaster strain transgenic for HIV-tat gene(Battaglia et al., 2001),
- Model Pathogens:
- Description: To analyze the mechanism of Tat-mediated HIV pathogenicity, we produced a Drosophila melanogaster strain transgenic for HIV-tat gene and induced the expression of the protein during Drosophila development. By in vitro and in vivo experiments, we demonstrated that Tat specifically binds to tubulin via the MAP-binding domain of tubulin, and that this interaction delays the polymerization of tubulin and induces a premature stop to microtubule-dependent cytoplasmic streaming. These results validate the use of Drosophila as a tool to study the molecular mechanism of viral gene products and suggest that Tat-tubulin interaction is responsible for neurodegenerative diseases associated with AIDS(Battaglia et al., 2001),
- Animals (non-human)
- Taxonomy Information:
- Species:
- Metazoa or Animalia (Website 64):
- Common Name: Metazoa or Animalia
- GenBank Taxonomy No.: 33208
- Description: In the light of recent confirmation that SIVcpz is the progenitor of HIV-1, it is not surprising that HIV-1 can readily be transmitted to common chimpanzees (Pan troglodytes)(Joag, 2000). HIV-2 and SIVsmm infections of macaques resemble SIVmac infections in most respects and in this review are considered as lying within the framework of the SIVmac/macaque model(Joag, 2000). Although macaques have been predominantly used in models based on viruses of the SIVsmm/HIV-2/SIVmac group, these viruses can also infect baboons (Papio cynocephalus) and models have been developed using this species(Joag, 2000). Perhaps the most promising and favorable alternative is the rat. A rat model for HIV-1 infection would offer many of the same advantages as a murine model, including low cost, small size, and a reasonably well-characterized immune system. With some difficulty, rats are also susceptible to transgenic manipulation, enabling selective expressing of human genes that may be essential for completing of the full HIV-1 replicative cycle(van Maanen and Sutton, 1998). The laboratory rabbit has been described as being susceptible to HIV-1 infection but very large doses of virus were used for inoculation, virus was difficult to detect and these initial results have not been successfully repeated in other studies. These shortcomings render the normal laboratory rabbit a poor animal model of HIV infection(Dunn et al., 1995). The development of a murine model for HIV-1 disease would provide a number of advantages over the primate models currently in use(van Maanen and Sutton, 1998). We used Drosophila melanogaster as a model to investigate the mechanism underlying the pathological effects of the HIV-Tat protein(Battaglia et al., 2001).
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Phinet: Pathogen-Host Interaction Network
Not available for this pathogen.
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Lab Animal Pathobiology & Management
NA
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Dennis Kunkel Microscopy: Dennis Kunkel Microscopy, Inc
Diagnostic Kit Insert - HIVAB EIA: HIVAB HIV-1/HIV-2 (rDNA) EIA
Diagnostic Kit Insert - Western Blotting: CAMBRIDGE BIOTECH HIV-l WESTERN BLOT KIT
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Data Provenance and Curators:
PathInfo:
Lewis Bryan
HazARD: (for the section of Lab Animal Pathobiology & Management)
PHIDIAS: Yongqun "Oliver" He
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