758-W.

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HIV-1 Diversity in France, 1999-2001: Molecular Characterization of non-B HIV-1 Subtypes and Potential Impact on ARV Susceptibility
H. Fleury*1, A. Caumont1, M. Faure1, J. C. Plantier2, P. Roques3, E. Couturier4, and F. Simon2 for the French ANRS Group
1 Lab. de Virologie, Bordeaux; 2 Lab. de Virologie, Rouen; 3CEA Fontenay aux Roses; and 4Inst. de Veille Sanitaire, Saint Maurice, France
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Background: Little information is available on the impact of HIV-1 non-B genetic diversity on antiretroviral (ARV) susceptibility. Our aims were to characterize HIV-1 non-B strains circulating in France in a population with a known date of infection; to assess the prevalence of recombination; and to study the polymorphism of reverse transcriptase (RT) and protease genes in terms of potential drug resistance.
Methods: All adults who tested HIV-1 positive on Western blot for the first time between 1999 and 2001 were eligible. Data on age, sex, country of birth, HIV-transmission group, dates of the last negative and first positive HIV tests (time limit less than 24 months), and clinical stages were collected. Serotyping was performed with a peptide subtype-specific enzyme immunoassay on each plasma sample. All non-B samples were selected, and a genotypic study was then carried out. The nucleotide sequences of the RT, protease and env C2/V3 genes were studied from PBMC samples. HIV-1 subtype was determined by phylogenetic analysis. Polymorphism and ARV drug resistance mutations were noted in the RT and protease genes.
Results: Among 68 samples of non-B from whom subtype results were available were 28 CRF02_AG, 5 D, 4 CRF01_AE, 3 A, 3 F1, 2 C, 2 G, 2 CRF06, 1 F1, 1 F2, 1K; 8 samples were B not detected by serotyping. 9 isolates were considered as intersubtype recombinants: 1 A/CRF06, 1 A/CRF03, 2 AG/CRF06, 1 J/A, 1 CRF04/G, 1 F2/B and 2 isolates seemed to be even more complex. Among all non-B samples, no primary resistance mutation to protease inhibitors (PI) was detected. The polymorphisms K20I and M36I were highly prevalent in subtypes CRF02, G, J, F2, and CRF06. No major resistance mutation to RT inhibitors was reported, except for 1 D (M184I), 1 J (T69N, K70R), and 1 A isolates (K103N). Among B isolates found by genotyping, 2 were highly resistant to NRTI and NNRTI, and 1 was resistant to PI, suggesting transmission of highly resistant viruses transmission to patients.
Conclusions: Despite an extensive variation of prot and RT polymorphisms compared to subtype B viruses, most of these non-B viruses seemed to have a full susceptibility to ARV. The same study allowed us to point out the high genetic diversity of non-B isolates, including intersubtype recombinants, within the French population.
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