title: Week 144 resistance analysis of elvitegravir/cobicistat/emtricitabine/tenofovir DF versus atazanavir+ritonavir+emtricitabine/tenofovir DF in antiretroviral-naïve patients.
abstract: OBJECTIVE
  To describe baseline and emergent HIV-1 resistance to elvitegravir/ cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF) and ritonavir-boosted atazanavir/emtricitabine/tenofovir DF (ATV+RTV+FTC/TDF) in HIV-1-infected, treatment-naïve subjects through 144 weeks.
  
  
  METHODS
  This was a randomized, double-blind, phase 3 study. HIV-1 protease (PR) and reverse transcriptase (RT) were sequenced at screening. Genotypic and phenotypic analyses were performed at virologic failure confirmation and retrospectively at baseline for PR, RT, and integrase (IN) for patients with virologic failure through week 144.
  
  
  RESULTS
  In the EVG/ COBI/FTC/TDF group through week 144, HIV-1 from 8 patients (2.3%; 8/353 treated patients) developed primary IN strand transfer inhibitor (INSTI) (n = 6) and/or nucleoside RT inhibitor (NRTI) resistance substitutions (n = 7). The emergence of resistance decreased after the first year, with 5 patients developing HIV-1 resistance through week 48, 1 from weeks 48-96, and 2 from weeks 96-144. Emergent substitutions were E92Q, N155H, or Q148R (n = 2 each) and T66I or T97A (n = 1 each) in IN and M184V/I (n = 7) and K65R (n = 1) in RT. All 8 isolates had reduced susceptibility to EVG, FTC, or TDF. Virus with EVG phenotypic resistance showed cross-resistance to raltegravir. In the ATV+RTV+FTC/TDF group, HIV-1 from 2 patients (0.6%; 2/355 treated patients; both at week 144) developed the resistance substitution M184V/I in RT.
  
  
  CONCLUSIONS
  Resistance development to EVG/COBI/FTC/TDF was infrequent (2.3%) through 144 weeks of therapy and decreased over time, consistent with durable efficacy.
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Rima
authors.initials: R
authors.lastname: Kulkarni
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Abram
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: McColl
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Barnes
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Fordyce
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Javier
authors.initials: J
authors.lastname: Szwarcberg
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Cheng
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: White
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D002219:Carbamates / Q000008:administration & dosage / Q000627:therapeutic use; D000069547:Cobicistat; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D006678:HIV / Q000187:drug effects / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D015363:Quinolones / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D000068698:Tenofovir; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D015363:Quinolones; D012367:RNA, Viral; D013844:Thiazoles; D003841:Deoxycytidine; C509700:elvitegravir; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D000069547:Cobicistat; D019438:Ritonavir
keywords: HIV-1; cobicistat; elvitegravir; emtricitabine; resistance; tenofovir