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Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients

Citation:

Soulie C, Santoro MM, Charpentier C, Storto A, Paraskevis D, Di Carlo D, Gennari W, Sterrantino G, Zazzi M, Perno CF, et al. Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients. J Antimicrob ChemotherJ Antimicrob ChemotherJ Antimicrob Chemother. 2019;74:614-617.

Abstract:

BACKGROUND: Doravirine is a novel HIV-1 NNRTI recently shown to be non-inferior to both darunavir/ritonavir and efavirenz in combination therapy with two NRTIs in treatment-naive patients. Doravirine has an in vitro resistance profile that is distinct from other NNRTIs and retains activity against viruses containing the most frequently transmitted NNRTI mutations. OBJECTIVES: The aim of this study was to examine the prevalence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients in Europe. METHODS: From 2010 to 2016, 9764 treatment-naive patients were tested for NNRTI antiretroviral drug resistance by bulk sequencing in Greece, Italy and France. We studied the prevalence of doravirine resistance-associated mutations previously identified in vitro: V106A/M, V108I, Y188L, V190S, H221Y, F227C/L/V, M230I/L, L234I, P236L, Y318F and K103N/Y181C. RESULTS: Among 9764 sequences, 53.0% and 47.0% of patients had B and non-B subtypes, respectively. Overall, the presence of at least one doravirine resistance-associated mutation (n = 137; 1.4%) or the K103N/Y181C mutations (n = 5; 0.05%) was very rare. The most prevalent mutations were V108I (n = 62; 0.6%), Y188L (n = 18; 0.2%), H221Y (n = 18; 0.2%) and Y318F (n = 23; 0.2%). The frequency of doravirine resistance-associated mutations was similar between B and non-B subtypes. In comparison, the prevalence of rilpivirine, etravirine, nevirapine and efavirenz resistance was higher whatever algorithm was used (ANRS: 8.5%, 8.1%, 8.3% and 3.9%, respectively; Stanford: 9.9%, 10.0%, 7.5% and 9.4%, respectively). CONCLUSIONS: The prevalence of doravirine resistance-associated mutations is very low in antiretroviral-naive patients. These results are very reassuring for doravirine use in naive patients.

Notes:

1460-2091Soulie, CathiaSantoro, Maria MercedesCharpentier, CharlotteStorto, AlexandreParaskevis, DimitriosDi Carlo, DomenicoGennari, WilliamSterrantino, GaetanaZazzi, MaurizioPerno, Carlo FedericoCalvez, VincentDescamps, DianeCeccherini-Silberstein, FrancescaMarcelin, Anne-GenevièveJournal ArticleResearch Support, Non-U.S. Gov'tEnglandJ Antimicrob Chemother. 2019 Mar 1;74(3):614-617. doi: 10.1093/jac/dky464.