Genetic diversity of HIV in Africa: Impact on diagnosis, treatment, vaccine development and trials

AIDS (Impact Factor: 5.55). 01/2004; 17(18):2547-60. DOI: 10.1097/01.aids.0000096895.73209.89
Source: PubMed
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    • "HIV-1 subtype G infects approximately 1.5 million individuals, primarily in west Africa, but also on the Iberian peninsula, Cuba and, more rarely, other global locations (Hemelaar et al., 2011). Cameroon is located in west central Africa, the epicentre of the HIV epidemic, where many HIV-1 types and subtypes co-circulate (Peeters et al., 2003; Tebit and Arts, 2011). Despite having a relatively low HIV prevalence, Cameroon has one of the most genetically diverse HIV epidemics in the world, with a very large variety of HIV-1 circulating recombinant forms (CRFs) (Brennan et al., 2008; Carr et al., 2010; Ceccarelli et al., 2012; Soares et al., 2010; Tongo et al., 2013; Torimiro et al., 2009). "
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    ABSTRACT: HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 group M (HIV-1M) epidemic in central/west Africa. Here, we analysed new subtype G env sequences sampled from 8 individuals in Yaoundé, Cameroon during 2007-2010, together with all publically available subtype G-attributed full-length env sequences with known sampling dates and locations. We inferred that the most recent common ancestor (MRCA) of the analysed subtype G env sequences most likely occurred in ∼1953 (95% Highest Posterior Density interval (HPD) 1939-1963): about 15years earlier than previous estimates. We found that the subtype G env phylogeny has a complex structure including seven distinct lineages, each likely dating back to the late 1960s or early 1970s. Sequences from Angola, Gabon and the Democratic Republic of Congo failed to group consistently in these lineages, possibly because they are related to more ancient sequences that are poorly sampled. The circulating recombinant form (CRF), CRF06_cpx env sequences but not CRF25_cpx env sequences are phylogenetically nested within the subtype G clade. This confirms that the CRF06_cpx env plausibly was derived through recombination from a subtype G parent, and suggests that the CRF25_cpx env was likely derived from an HIV-1M lineage related to the MRCA of subtype G that has remained undiscovered and may be extinct. Overall, this fills important gaps in our knowledge of the early events in the spread of HIV-1M. Copyright © 2015. Published by Elsevier B.V.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 07/2015; 35. DOI:10.1016/j.meegid.2015.07.017 · 3.02 Impact Factor
    • "These primates are frequently hunted as agricultural pests and sold as bush-meat in various parts of West Africa, which may provide the likely route of transmission to humans [40]. Of the eight distinct groups of HIV-2 (A–H), only groups A and B have spread throughout West Africa, particularly Guinea- Bissau and Senegal [16] [41], and Cote d'Ivoire [42], respectively. Other groups have been identified in single individuals with limited secondary spread [12] "
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    ABSTRACT: Despite considerable similarities in genomic organization and sequence, the natural history of infection with HIV-2 is quite distinct from HIV-1, with low rates of transmission and a surprisingly high proportion of long-term non-progressors.•Unlike HIV-1, most HIV-2-infected subjects generate high titres of broadly neutralizing antibodies that neutralize primary HIV-2 isolates.•Two cysteine residues in the V2 loop of the HIV-2 envelope, uniquely found in HIV-2 and SIVsm, may stabilize the envelope trimer structure.•The V3 and V4 loops of HIV-2 envelope have fewer glycosylation sites than HIV-1, which may lead to increased exposure to neutralising antibody.•The V3 loop of R5 variants of HIV-2 shows strict length conservation: the longer V3 loop of X4 variants is more resistant to neutralisation.•Despite high rates of intra-patient envelope diversity, HIV-2 variants that are resistant to neutralization do not appear to accumulate to fixation.•A better understanding of the factors that lead to such a potent broadly neutralising antibody response in HIV-2 infection could provide important clues for HIV vaccine design.
    Immunology Letters 11/2014; 163(1). DOI:10.1016/j.imlet.2014.10.028 · 2.51 Impact Factor
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    • "These assays are designed specifically for HIV-1 subtype B strains predominant in North America and Europe. Hence, genetic diversity of non B subtype HIV-1 strains prevalent in Africa and Asia pacific region poses challenge for use of these kits in such geographical regions [13]. This has led to continuous efforts to develop homebrew HIV-1 drug resistance genotyping assays across the world with varying success [14]–[16]. "
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    ABSTRACT: Human Immunodeficiency Virus-1 (HIV-1) drug resistance genotyping assay is a part of clinical management of HIV-1 positive individuals under treatment with highly active antiretroviral therapy (HAART). Routine monitoring of drug resistance mutations in resource limited settings like India is not possible due to high cost of commercial drug resistance assays. In this study we developed an in-house, cost effective HIV-1 drug resistance genotyping assay for Indian patients and validated it against the US-FDA-approved ViroSeq HIV-1 drug resistance testing system. A reference panel of 20 clinical samples was used to develop and validate the assay against ViroSeq HIV-1 drug resistance testing system which was subsequently used to genotype a clinical panel of 225 samples. The Stanford HIV database was used to identify drug resistant mutations. The analytical sensitivity of the assay was 1000 HIV-1 RNA copies/ml of plasma sample while precision and reproducibility was 99.68±0.16% and 99.76±0.18% respectively. One hundred and one drug resistant mutations were detected by the in-house assay compared to 104 by ViroSeq system in the reference panel. The assay had 91.55% success rate in genotyping the clinical panel samples and was able to detect drug resistant mutations related to nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse-transcriptase inhibitor (NNRTI) as well as protease inhibitor (PI) classes of antiretroviral drugs. It was found to be around 71.9% more cost effective compared to ViroSeq genotyping system. This evaluation of the assay on the clinical panel demonstrates its potential for monitoring clinical HIV-1 drug resistance mutations and population-based surveillance in resource limited settings like India.
    PLoS ONE 08/2014; 9(8):e105790. DOI:10.1371/journal.pone.0105790 · 3.23 Impact Factor
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