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Prevalence of Minority Resistant Variants in HIV-2 Naïve Patients: ANRS CO5 Cohort
Alexandre Storto1; Benoit Visseaux2; Gilles Collin1; Catherine Fagard3; Marine Naudin4; Florence Damond1; Marie-Aude Khuong5; Sophie Matheron1; Diane Descamps1;Charlotte Charpentier2
1Hosp Bichat-Claude Bernard, Paris, France;2INSERM UMR 1137, Paris, France;3CMG-EC INSERM U897, Bordeaux, France;4CMG-EC de l'INSERM U897, Bordeaux, France;5Hosp Delafontaine, Paris, France
To assess the prevalence of minority resistant variants (MRV) and X4-minority variants in antiretroviral-naïve HIV-2-infected patients included in the French HIV-2 Cohort (ANRS CO5).
Antiretroviral-naïve HIV-2-infected patients with detectable plasma viral load (VL) (>100 c/mL) were assessed. We performed UltraDeep Sequencing (UDS) (Roche 454® Life Sciences) in protease (PR) and reverse transcriptase (RT) regions issued from plasma viruses. Only mutations >1% were considered and interpreted with HIV-2 ANRS list (Charpentier et al., 2015). HIV-2 tropism was assessed by UDS of V3 loop region. Tropism of each sequence read was interpreted with HIV-2 major determinants of CXCR4 co-receptor use (L18X, V19K/R, V3 global net charge, insertions at position 24).
47 patients were assessed (median age: 48 years [IQR=36-57], 61% women, 68% originating from West Africa, 12% at CDC-C stage). At time of sampling, median CD4 cell count was 326/mm3 (IQR=215-438) and median VL was 2130 c/mL (IQR=816-4495). 67% of patients were infected with HIV-2 group A and 33% with group B. Protease and RT UDS was successful in 41 (87%) and 38 (81%) samples, respectively. Prevalence of virus with PR or RT drug resistance mutations (DRM) using 1% and 20% detection threshold was 17.1% (95%CI=5.5-28.7) and 7.3% (95%CI=0.0-15.4), respectively. DRM detected at the 20% detection threshold were M184V in one case and N69S in two cases. MRV exhibiting at least 1 NRTI DRM were detected in 1 patient (2.6%, 95%CI=0.0-6.8), showing the mutation N69S in a proportion of 1.4%. MRV exhibiting at least 1 PI DRM were detected in 4 patients (9.8%, 95%CI=0.7-18.9): (i) two I50V-mutated MRV (1.6% and 1.0%); (ii) one V47A (1.0%); and (iii) one with both I50V and I54L (1.2% and 1.1%, respectively). Tropism was assessed in 19 samples (mean number of reads=7591) showing 2 samples (11%) exhibiting X4-tropic viruses in more than 50% of the reads. Among the 17 remaining samples, X4-minority variants were detected in 11 (65%) in a median proportion of 0.41% (IQR=0.33-0.76).
In this first study assessing the prevalence of MRV in HIV-2 infection, we observed a two to three-fold higher prevalence of DRM in antiretroviral-naive patients when 1% detection threshold of mutations was used compared to 20% threshold. In addition, X4-minority variants were detected in the majority of patients.