Analysis of early resistance development at the first failure timepoint in elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate-treated patients

Abstract

Objectives: The patterns of emergent HIV-1 drug resistance in patients failing a single-tablet regimen consisting of elvitegravir, boosted by cobicistat, plus emtricitabine and tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) include mutations in HIV-1 reverse transcriptase (RT) and integrase (IN). The order of development of mutations at early virological failure has not been described. The aim of this study was to determine the first resistance mutations to emerge during virological failure on EVG/COBI/FTC/TDF. Patients and methods: Population sequencing was conducted at the first virological failure timepoint with HIV-1 RNA ≥ 400 copies/mL for each of the 18 patients with emergent resistance in the EVG/COBI/FTC/TDF arms of two randomized, double-blind, Phase 3 studies of EVG/COBI/FTC/TDF through Week 144. Results: At first failure compared with confirmed virological failure, 4 of the 18 patients had no detectable resistance mutation in their virus and only 51% of the RT and IN mutations were detected overall. M184V/I in RT was the first mutation to appear in many cases (n=6) and was then followed by additional mutations in RTand IN. No case with development of resistance to the IN strand-transfer inhibitor prior to the development of M184V/I was detected. Conclusions: The analysis of first failure found fewer patients with emergent resistance and fewer resistance mutations than the standard analysis at the later confirmation of virological failure. The early detection of resistance may preserve later treatment options.