ABSTRACT
OBJECTIVE: The goal of the OSCAR programme is to evaluate the performances of genotypic HIV-1 tropism testing in clinical practice using the enhanced sensitivity version of Trofile (ESTA) as reference-assay. METHODS: HIV-1 coreceptor-usage was assessed using plasma samples from 406 HIV-1 infected patients by ESTA and by gp120 V3 population-sequencing followed by Geno2pheno (set at a False Positive Rate [FPR] of 10% and 5%). RESULTS: ESTA was successful in 365 (89.9%) samples indicating R5 in 254 (69.6%), and DM/X4 in 111 (30.4% of samples (104 [28.5%] DM and 7 [1.9%] X4). Genotypic-testing successfully assessed viral tropism for all 406 samples, including the 41 with undetermined result by ESTA. Genotypic-tropism testing at a FPR of 5% and 10% was 81.1% and 78.4% concordant with ESTA, respectively. Despite a sensitivity of 48.7% and 55.9% at a FPR of 5% and 10%, respectively, a high concordance (specificity: 95.3% for FPR of 5% and 88.2% for FPR of 10%) between genotypic-tropism testing and ESTA was reached in the detection of R5-tropic viruses. CONCLUSION: Our results are in line with other European studies, and support the routine use of genotypic tropism testing in clinical-settings for monitoring of HIV-1 infected patients candidate to or failing CCR5-antagonists.
Subject(s)
CCR5 Receptor Antagonists , HIV Infections/virology , HIV-1/genetics , Receptors, Virus/genetics , Viral Tropism , Female , Genotype , HIV Envelope Protein gp120/chemistry , HIV Envelope Protein gp120/genetics , HIV Infections/genetics , HIV Infections/metabolism , HIV-1/classification , HIV-1/isolation & purification , HIV-1/physiology , Humans , Male , Protein Structure, Tertiary , Receptors, CCR5/genetics , Receptors, CCR5/metabolismABSTRACT
A broad and rapidly changing HIV Type 1 (HIV-1) diversity has been reported from different populations in Cameroon since the early epidemic. Our understanding of HIV-1 dynamics can be improved by a systematic surveillance in Cameroon as accessibility and use of antiretroviral drugs increase. To contribute to this, we genotyped 30 samples by sequencing the protease and reverse transcriptase (proRT) genes of HIV-1. Phylogenetic analysis of the HIV-1 proRT sequences using the MEGA3 software showed that 26 (86.7%) were recombinant forms which included 20 (66.7%) circulating recombinant forms: CRF02_AG, (50%), CRF06_cpx (3.3%), CRF11 _cpx (10%) and CRF37_cpx (3.3%), and 6 unique recombinant forms (URF, 20%). Two of the six URFs were second generation recombinants and 4 contained unclassified segments. HIV-1 subtypes A1 (3.3%), C (3.3%) and D (6.7%) were also identified. Although partial sequences of HIV-1 genome were analysed, our results indicate that recombinant HIV-1 variants predominate in the AIDS epidemic in Cameroon. With the widespread use of antiretroviral drugs in Cameroon and the circulation of several HIV-1 variants within this population, the emergence of recombinants with unknown diagnostic and clinical consequences is a concern.
Subject(s)
Disease Outbreaks , Genetic Variation , HIV Infections , HIV-1/genetics , Recombination, Genetic , Adolescent , Adult , Cameroon/epidemiology , Child , Child, Preschool , Female , Genotype , HIV Infections/epidemiology , HIV Infections/genetics , HIV Infections/virology , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1/classification , Humans , Male , Middle Aged , Phylogeny , Sequence Analysis, DNAABSTRACT
Enfuvirtide is the first of a new class of antiretroviral drugs that inhibits HIV entry. It is a 36 amino acid synthetic peptide that mimics the HR2 region of the HIV-1 gp41, preventing the fusion of viral and cellular membranes. Up to now, enfuvirtide was designed based on the HIV-1 B-subtype gp41, and resistance mutations to the fusion inhibitor have been investigated primarily in individuals infected with this subtype. To fill the gap, we analyzed the full length gp41 protein sequence of HIV-1 non-B strains from individuals receiving enfuvirtide-containing regimens. No primary resistance to the enfuvirtide binding domain (36-45 residues) was found. Resistance mutations were detected at follow-up visits and were comparable to those described among B-subtype HIV-1-infected patients; no sequence changes were detected in crucial HR1/HR2 gp41 sites such as the cytotoxic T lymphocyte epitope, cysteine loop, ectodomain, and 5-helix interaction and binding region.
