title: Week 144 resistance analysis of elvitegravir/cobicistat/emtricitabine/tenofovir DF versus efavirenz/emtricitabine/tenofovir DF in antiretroviral-naive patients.
abstract: BACKGROUND
  Here, the baseline and emergent resistance to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) versus efavirenz (EFV)/FTC/TDF in HIV-1-infected antiretroviral-naive adults through 144 weeks from the randomized, ongoing, Phase III study GS-US-236-0102 is described.
  
  
  METHODS
  HIV-1 protease (PR) and reverse transcriptase (RT) were sequenced at screening; patients with HIV-1 resistant to EFV, FTC or TDF were excluded. Genotypic/phenotypic analyses were performed at virological failure confirmation and baseline for PR, RT and integrase (IN) for patients with virological failure and for patients with HIV-1 RNA≥400 copies/ml at weeks 48, 96, 144 or early study drug discontinuation. Retrospective, baseline, IN genotyping was conducted for EVG/COBI/FTC/TDF patients.
  
  
  RESULTS
  In the EVG/COBI/FTC/TDF group through week 144, HIV-1 from 10 patients (2.9%; 10/348 treated patients) developed primary IN strand transfer inhibitor (n=9) and/or nucleoside RT inhibitor resistance substitutions (n=10). The emergence of resistance decreased over time with 8, 2 and 0 patients developing HIV-1 resistance through week 48, post-week 48-96 and post-week 96-144, respectively. Emergent substitutions were E92Q (n=7), N155H (n=3), Q148R (n=1) and T66I (n=1) in IN, and M184V/I (n=10) and K65R (n=4) in RT. All 10 isolates had reduced susceptibility to EVG, FTC or TDF. Virus with EVG phenotypic resistance had cross-resistance to raltegravir. In the EFV/FTC/TDF group, virus from 14 patients (4.0%; 14/352 treated patients; 4 during weeks 96-144) developed a resistance substitution to EFV (n=14; K103N: n=13), FTC (M184V/I: n=4) or TDF (K65R: n=3).
  
  
  CONCLUSIONS
  Resistance development to EVG/COBI/FTC/TDF was infrequent through 144 weeks of therapy and decreased over time, consistent with durable efficacy.
authors.affiliation: Clinical Virology, Gilead Sciences, Inc., Foster City, CA, USA. Kirsten.White@gilead.com.
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: White
authors.forename: Rima
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Damian J
authors.initials: DJ
authors.lastname: McColl
authors.forename: Martin S
authors.initials: MS
authors.lastname: Rhee
authors.forename: Javier
authors.initials: J
authors.lastname: Szwarcberg
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Cheng
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
mesh_terms: D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000008:administration & dosage; D000069547:Cobicistat / Q000008:administration & dosage; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D000068679:Emtricitabine / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D015363:Quinolones / Q000008:administration & dosage; D000068698:Tenofovir / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D015363:Quinolones; C509700:elvitegravir; D000068698:Tenofovir; D000068679:Emtricitabine; C098320:efavirenz; D000069547:Cobicistat