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HIV-1 is a chimpanzee virus which was transmitted to humans by several zoonotic events resulting in infection with HIV-1 groups M-P, and in parallel transmission events from sooty mangabey monkey viruses leading to infections with HIV-2 groups A-H. Both viruses have circulated in the human population for about 80 years. In the infected patient, HIV mutates, and by elimination of some of the viruses by the action of the immune system individual quasispecies are formed. Along with the selection of the fittest viruses, mutation and recombination after superinfection with HIV from different groups or subtypes have resulted in the diversity of their patterns of geographic distribution. Despite the high variability observed, some essential parts of the HIV genome are highly conserved. Viral diversity is further facilitated in some parts of the HIV genome by drug selection pressure and may also be enhanced by different genetic factors, including HLA in patients from different regions of the world. Viral and human genetic factors influence pathogenesis. Viral genetic factors are proteins such as Tat, Vif and Rev. Human genetic factors associated with a better clinical outcome are proteins such as APOBEC, langerin, tetherin and chemokine receptor 5 (CCR5) and HLA B27, B57, DRB1*1303, KIR and PARD3B., (Copyright © 2012 S. Karger AG, Basel.)

Antiretroviral drug resistance is mostly linked to a complex interaction of several amino acids with variable importance or a single amino acid. To facilitate the interpretation of observed mutation patterns, hospital university centers have developed several interpretation systems. All the currently available interpretation algorithms evolved, are being continuously updated and have been improved during the last decade. Some discrepancies are still evident that are partially smoothened by link of the individual programs with other systems. After the interpretation of HIV-1 group M subtype B mutations, a refined algorithm for the other group M subtypes was developed followed by the interpretation of HIV-1 group O and HIV-2 mutations. The process of improvement is ongoing, due to the better understanding and interpretation of single and cluster mutations and the availability of new antiretroviral substances. The knowledge gained from the experience of HIV drug resistance testing has been used to establish the interpretation of HBV polymerase mutations and will be extended for the treatment of HCV infected with protease inhibitors. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

BACKGROUND: In February 2007, a 63-year-old man underwent surgery. Retrospective testing with nucleic acid testing (NAT) showed that the patient was human immunodeficiency virus Type 1 (HIV-1) positive 10 days after transfusion. The transfusion-transmitted infection had been identified by a donor-related lookback started in April 2007 after anti-HIV seroconversion. METHODS: Sequence analysis was performed in the gag-pol region as well as in the V3 loop env region. Archived plasma from the transmitting donation was investigated for the individual-donation NAT with the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test (Roche CAP/CTM HIV-1 test) and for HIV antigen/antibody combination testing (Abbott Architect). Additional testing was done on the donor's follow-up sample and on the recipient's sample. RESULTS: The Roche CAP/CTM HIV-1 test failed to detect viral RNA by minipool NAT in the index donation (April 2007) as well as in the donation that caused the infection (January 2007). Phylogenetic analysis showed a very high genetic similarity among viral sequences from both donor and recipient, proving the HIV-1 transmission by sequence data. CONCLUSION: This case represents the first documented HIV-1 transmission by transfusion of red blood cells after mandatory introduction of HIV-1 NAT for blood screening in Germany. Low viral load and mismatches in the primer/probe region might explain the detection failure of the NAT screening assay. A certain risk remains that new virus variants contain mutations at positions critical for amplification or detection of viral genomes. An option to reduce the risk of a detection failure by NAT is the simultaneous use of several conserved regions as amplification targets. [ABSTRACT FROM AUTHOR]

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Genetic variation among HIV isolates creates challenges for their detection by serologic and genetic techniques. To characterize the sequence variation and its correlation to serologic diversity of HIV-1 Group O and HIV-2 isolates, samples were identified by differential reactivity in selected commercial and research assays. Analysis of sera from Equatorial Guinea (EG) led to identification of 4 HIV-1 Group O variants. Viral RNA, extracted from these samples was used to PCR amplify overlapping sequences of the entire envelope gene using multiple primer pairs. Sequence analysis indicated that the V3 loop nucleotide and protein sequences aligned more closely with HIVANT70 compared to other Group O sequences. The amino acid sequences at the octameric tip of the V3 loop were RIGPLAWY, RIGPMAWY, or GLGPLAVY. The tetrameric tip GPLA is represented only once in the published 1994 HIV database (Los Alamos) but was present in 2 of 4 of EG samples. The immuno-dominant region (IDR) sequences derived from EG sera were unique in that none of the sequences were completely homologous to other HIV-1 group O variants. Further, the HIV-1 group O sequence variation could be correlated with differential serologic reactivity using IDR peptides. Compared to HIV-1, the sequence information on HIV-2 isolates is relatively limited, though the HIV-2 isolates also show genetic variation similar to HIV-I. To further establish a correlation between the genetic diversity and serologic detection of HIV-2, plasma samples from Western Africa were evaluated. Eight samples were selected based on weak serologic reactivity to env proteins. PCR amplification and sequence analysis of the gag;, env V3 loop, and env IDR regions indicated that the samples could be classified as subtypes A (4 samples), B (3 samples) and D (1 sample). Across the subtypes, there was conservation in the IDR region of the sequence WGCAFRQVCHT. This region is absolutely conserved among the majority of currently known HIV-2 and related SIV viruses (1994 HIV database). One subtype B sample had a unique sequence immediately adjacent to the IDR, however, this did not change the serologic detection using a HIV-2 IDR specific monoclonal antibody. [ABSTRACT FROM AUTHOR]

The article discusses the updated standardized human immunodeficiency virus type 2 (HIV-2) drug-resistance interpretation. Topics discussed include protease mutations selected at the time of virological failure in patients receiving a protease inhibitor-based treatment, availability of some data on atazanavir-based therapy and no major change for raltegravir concerning integrase inhibitors.

Abstract: Given the worldwide increasing spread of HIV-1 genetic variants, it is mandatory that assays used for nucleic acid testing for HIV-1 detect all existing groups and subtypes of HIV-1. In this report the development and evaluation of a quantitative real-time HIV-1 RT-PCR assay that targets a conserved region within the pol integrase domain is described. As an internal control reaction, endogenous glyceraldehyde-3-phosphate-dehydrogenase transcripts were detected in a multiplex configuration. The detection limit (95% cut-off value) was determined by probit analysis and calculated as 281IU/ml of HIV-1 RNA. Within-run and between-run coefficients of variation were below 15 and 27%, respectively, indicating high reproducibility. The described assay detected all tested HIV-1 isolates representing groups M, O and N. Within group M, quantitative test results correlated well with viral loads as determined by the automated Abbott RealTime™ HIV-1 assay. Based on the testing of 1206 confirmed HIV-1 RNA negative blood donor samples, assay specificity was found to be 100%. The rate of inhibition was 0.37%. The described HIV-1 real-time RT-PCR was validated according to regulatory guidelines and is applicable to the screening of blood donors as well as the determination of HIV-1 viral load. [Copyright &y& Elsevier]

In this report, we describe the construction and characterization of the first full-length infectious molecular clone from the Cameroonian HIV-1 group O primary isolate MVP8913. Virus obtained after transfection of the proviral clone pCMO2.3 replicated to levels comparable to its parental isolate in the human T-cell line PM-1, although replication was reduced by fivefold in peripheral blood mononuclear cells (PBMC) and was barely detectable in primary monocyte-derived macrophages (MDM). Phylogenetic analysis of the complete proviral sequence revealed a closer relationship to ANT70 than to MVP5180, the two prototypic group O primary isolates. All reading frames for structural and accessory genes were open except for vpr that contained an in-frame stop codon. In the nef gene, a mutation disrupting the functionally important myristoylation signal was observed. Repairing the defect in nef enhanced replication in PBMC and MDM, although repairing the vpr defect only affected replication in MDM, consistent with the known phenotypes of vpr and nef mutants in HIV-1 group M viruses. Repairing both vpr and nef showed an additive effect, but the resulting virus was still impaired compared to the parental isolate. This defect was overcome when the gag-pol coding region was exchanged for that from another O-type isolate giving rise to the proviral clone pCMO2.5. Virus obtained from pCMO2.5 replicated with similar kinetics as the parental O-type isolate in both PBMC and MDM, making this proviral clone a valuable tool for further studies on functional characteristics of HIV-1 group O viruses. [Copyright &y& Elsevier]

We report the second human immunodeficiency virus (HIV) belonging to the new HIV type 1 (HIV-1) group P lineage that is closely related to the simian immunodeficiency virus found in gorillas. This virus was identified in an HIV-seropositive male hospital patient in Cameroon, confirming that the group P virus is circulating in humans. Results from screening 1,736 HIV-seropositive specimens collected in Cameroon indicate that HIV-1 group P infections are rare, accounting for only 0.06% of HIV infections. Despite its rarity, group P shows evidence of adaptation to humans. [ABSTRACT FROM AUTHOR]