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PREVALENCE AND IMPACT OF PRETREATMENT DRUG RESISTANCE IN THE ANRS 12249 TASP TRIAL
Anne Derache1, Collins C. Iwuji2, Siva Danaviah1, Anne-Geneviève Marcelin3, Vincent Calvez3, Tulio de Oliveira4, François Dabis5, Deenan Pillay1
1Africa Hlth Rsr Inst, Mtubatuba, South Africa,2Univ Coll London, UK, London, UK,3Pitie-Salpetriere Hosp, Paris, France,4Univ of KwaZulu-Natal, Durban, South Africa,5Univ de Bordeaux, Bordeaux, France
Increasing use of antiretroviral therapy (ART) in Test and Treat strategies may lead to higher levels of acquired and transmitted drug resistance (DR) and compromise ART efficacy for individual or population benefits. We assessed prevalence of pre-treatment DR (PDR) and impact on viral suppression (VS) [viral load (VL)<400 copies/mL] among ART naïve participants who initiated 1st-line ART within the ANRS 12249 cluster-randomized trial.
DR testing was done on samples from 1340 participants who were recently infected (RIn) during the trial or chronically infected (CIn) at entry (March 2012–June 2016). Pol gene Sanger sequencing was done on dried blood spots from 195 RIn participants who had not linked to HIV care. Full HIV genome sequencing using the MiSeq platform was done on plasma samples from 77 RIn and 1069 Cln participants who linked to care, of whom 838 initiated ART. Minority variants were called at a 2% level (Geneious and MiCall softwares). Cox regression was used to estimate hazard ratios (HR) for VS.
Overall PDR prevalence was 8,4% (95%CI=6,7-10%) and 17,8% (95%CI=15,1-20,5%) at 20% and 2% detection levels respectively; these proportions were similar between RIn and CIn participants. Among participants with PDR, 88% had only 1 or 2 DR mutations, associated with NNRTI resistance in 73% of the cases, and 61% were detected as a majority variant (>20%). 13,5% and 8,8% were associated with NRTI and PI resistance, respectively, with 90% of them being minority variants (<20%) for both NRTI and PI. Among RIn participants with PDR, 92% were associated with a single ARV class (mostly NNRTI). Among 838 adults initiating ART, median follow-up time on ART was 16 months (m); median time to VS was 3m (IQR 2.8-3.9). Cumulative VS at 12m was 97%. After adjusting for sex, age, baseline VL and adherence, there was no evidence that PDR was associated with VS (adjusted (a)HR 0.96, 95%CI 0.75-1.23 and aHR=1.12, 95%CI 0.89-1.42, for majority and minority variants, respectively, vs no mutations). High baseline VL (>100,000 vs <10,000) was associated with a decreased rate of VS (aHR 0.75; 0.62-0.91) and good adherence (≥95% vs <95%) was associated with an increased rate of VS (aHR 1.36; 1.11-1.66).
The prevalence of PDR approached 10% at >20% representation among RIn and CIn participants, while deep sequencing identified double the prevalence. Longer term follow up is needed to assess the lack of virological impact of PDR.