title: Analysis of early resistance development at the first failure timepoint in elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate-treated patients.
abstract: OBJECTIVE
  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.
  
  
  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 RT and 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.
authors.affiliation: Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA 94404, USA kirsten.white@gilead.com.
authors.forename: Kirsten
authors.initials: K
authors.lastname: White
authors.affiliation: Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA 94404, USA.
authors.forename: Rima
authors.initials: R
authors.lastname: Kulkarni
authors.affiliation: Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA 94404, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D017326:Clinical Trials, Phase III as Topic; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D017422:Sequence Analysis, DNA; D017211:Treatment Failure
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV-1; elvitegravir; emtricitabine; resistance; tenofovir