According to the French ANRS program for HIV-1 resistance surveillance, we estimated the prevalence of transmitted drug resistance associated mutations (TDRAMs) in primary infected patients (PHI) diagnosed in France in 2014-2016.
TDRAMs were sought in plasma samples from 373 patients in 2014, 388 in 2015 and 375 in 2016 (n=1136), from 46 clinical centers. Protease and reverse-transcriptase TDRAMs were identified from the 2009 Stanford Resistance Surveillance list; etravirine, rilpivirine and integrase mutations from the IAS and ANRS lists. Doravirine-associated mutations identified in vitro and defining DOR resistance in this study were: V106A, V106M, V108I, H221Y, F227L, F227C, F227V, M230I, L234I, P236L. The HIV envelope gene was sequenced and tropism was determined using the Geno2Pheno algorithm (FPR 10%). HIV-1 subtype was determined from the RT sequence.
Patients were mainly men (90%), having sex with men (73%), living in the Paris area (41%). At inclusion, the median CD4 cell count and plasma HIV-1 RNA were 480/µL (IQR: 330–637) and 5.5 log10 cp/mL (IQR: 4.7–6.4), respectively. By the Stanford list, the prevalence of virus with PR or RT RAMs was 10.6% (CI95% [8.92;12.59]). Prevalence of PI and NRTI resistance was 2.8% (CI95% [1.93;3.95]) and 5.1% [3.90;6.55]; prevalence of NNRTI resistance was 4.0% [2.90;5.26] or 10.2% [8.51;12.12] including etravirine and rilpivirine RAMs. INI RAMs were observed in 5.3% of samples [3.96;6.97]: L74M n=9, E92Q/G n=2, T97A n=14, E138K n=3, E157Q n=18, S230R n=2, R263K n=2. The double mutant E92Q+T97A was observed in 1 patient. The overall prevalence of sequences with at least 1 DOR associated mutation was 0.9% [0.42; 1.61]. The frequency of TDRAMs to NRTI, NNRTI, PI and INI was stable over time (Figure). At enrolment, 81/523 (15.5%) of samples harbored a X4/DM tropic virus. In a multivariate analysis, age (>30 years) was the only factor significantly associated with TDRAMs while baseline characteristics such as gender, transmission route, CD4 count, viral load, subtype and year of inclusion were not. The prevalence of non-B subtype increased from 37.1% in 2014 to 50.2% in 2016 (p<0.0027).
In France in the 2014/2016 period, the overall prevalence of TDRAMs was 10.6%, similarly to the previous surveys (going back to 1996 for PI and NRTI.) However, we describe a high level of NNRTI resistance (10.2%) including ETR and RPV (only 0.9% of resistance to doravirine) and a high prevalence of INI RAMs.