Prevalence of drug resistance in children recently diagnosed with HIV-1 infection in France (2006-17): Impact on susceptibility to first-line strategies

Abstract

Objectives: To describe the prevalence of transmitted drug resistance (TDR) among 84 children newly diagnosed with HIV in France in 2006-17. Methods: HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 Stanford list of mutations and the 2017 French National Agency for AIDS Research (ANRS) algorithm. A genotypic susceptibility score (GSS) was estimated for each first-line recommended ART combination. Results: Patients were mainly infected through mother-to-child transmission (MTCT) (73/84; 86.9%), but only 18 children (24.7% of vertically infected patients) were previously exposed to antiretroviral prophylaxis from MTCT. Non-B variants were identified in 90.5% (76/84) of patients. The frequency of TDR was 8.3% (7/84) using the 2009 Stanford list and 16.7% (14/84) using both the Stanford list and the 2017 ANRS algorithm. The prevalence of PI-, NRTI-, efavirenz/nevirapine-, etravirine/rilpivirine- and doravirine-associated RAMs was 0%, 3.6%, 6.0%, 11.9% and 2.4%, respectively. Single-, dual- and triple-class resistance was present in 15.5%, 1.2% and 0% of cases, respectively. Additionally, 3/60 (5%) strains had integrase inhibitor (INI)-related RAMs (an isolated E157Q mutation, which could mostly affect the susceptibility to raltegravir/elvitegravir rather than that to dolutegravir). Among the 18 children exposed to MTCT prophylaxis, RAMs were identified in only 1 case (5.6%). The proportion of fully active combinations (GSS=3) was ≥97.6%, ≥94.1%, ≥92.9% and ≥89.3%for PI-, INI-, efavirenz/ nevirapine- and rilpivirine-based regimens, respectively. Conclusions: The proportion of NRTI- and NNRTI-related TDR in children is lower in France than in low- and middle-income countries. However, we suggest favouring PI- or dolutegravir- over NNRTI-based combinations to treat newly diagnosed HIV-infected children, even in the absence of previous exposure to antiretroviral prophylaxis of MTCT.