Transmitted drug resistance in HIV-2-infected antiretroviral-naïve patients from the French HIV-2 cohort ANRS CO05

Background: To assess the prevalence of transmitted drug resistance mutations (DRM) and to determine viral tropism in HIV-2-infected patients included in the French HIV-2 Cohort (ANRS CO05).
Methods: 68 HIV-2-infected patients diagnosed between 2007 and 2011 issued from the French HIV-2 Cohort were assessed. All patients were antiretroviral-naïve with detectable HIV-2 RNA level (>100 copies/mL). Protease and RT were sequenced with an in-house method, and interpreted with HIV-2 ANRS, Rega and CHAIN-WP2 lists. HIV-2 tropism was assessed by gp105 sequencing, and interpreted with gp105 major determinants of CXCR4 co-receptor use we described (L18X, V19K/R, V3 global net charge, insertions at position 24). Absence of antiretroviral in samples harboring DRM or polymorphic substitutions was confirmed using UPLC-MS/MS.
Results: Median age of the patients was 42 years (IQR=34-47), among them 60% were women, 74% from West Africa, and 12% were in CDC-C disease stage. Median CD4 cell count was 412/mm3 (IQR=300-555). Median HIV-2 RNA level was 674 copies/mL (IQR=295-2522). Protease, RT, and gp105 sequencing was successful in 60 (88%), 47 (69%), and 40 (61%) samples. 65% of patients were infected with HIV-2 Group A and 35% with HIV-2 Group B. HIV-2 RNA tropism was as follows: 36 (90%) R5 and 4 (10%) X4/Dual-Mixed. No NRTI DRM was found. A PI DRM was found in 3 samples (5.0%, CI95=0.10-9.90%), evidencing the V47A in 2 cases and the I82F in the remaining one. In addition, we observed the N69D/S, V111I, and E219D RT substitutions in RT in 2 (4.2%), 4 (8.5%), and 1 (2.1%) samples, and the V71I, I89V, and L99F protease substitutions in 5 (8.3%), 7 (11.7%), and 3 (5.0%) samples. These substitutions are known to be polymorphic but were described as possibly playing a role in increasing level of resistance. Antiretroviral plasma concentrations were below the limit of quantification in all cases.
Conclusion: A prevalence of 5.0% of transmitted DRM was observed in these antiretroviral-naïve viremic HIV-2-infected patients issued from the French HIV-2 Cohort. This prevalence was in similar range to that reported in Ivory Coast or Portugal. Tropism analysis showed that 10% of HIV-2-infected patients displayed X4/Dual-Mixed virus.

C. Charpentier1,2, B. Visseaux1,2, A. Bénard3, G. Peytavin2,4, F. Damond1,2, C. Roy3, A. Taieb3, G. Chêne3, S. Matheron2,5, F. Brun-Vézinet1,2, D. Descamps1,2, French HIV-2 Cohort ANRS CO05
1AP-HP, Hopital Bichat Claude Bernard, Laboratoire de Virologie, Paris, France, 2EA 4409 Université Paris Diderot, Paris, France, 3INSERM U 897/ ISPED, Bordeaux Segalen University, Bordeaux, France, 4AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Pharmacologie, Paris, France, 5AP-HP, Hopital Bichat-Claude Bernard, Service des Maladies Infectieuses et Tropicales, Paris, France