title: Lower prevalence of drug resistance mutations at first-line virological failure to first-line therapy with atripla vs. tenofovir + emtricitabine/lamivudine + efavirenz administered on a multiple tablet therapy.
abstract: BACKGROUND
  Fixed-dose combination antiretroviral therapy administered as a single-tablet regimen (STR) may improve virologic suppression rates. The effect of STRs on development of resistance when virologic failure occurs on STRs is not known.
  
  
  OBJECTIVE
  To compare the rate of emergent drug resistance mutations (DRMs) on first-line therapy with coformulated tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/efavirenz (EFV) as an STR versus TDF, lamivudine (3TC) or FTC, and EFV given as non-STR.
  
  
  METHODS
  Patients from eight cohorts and four randomized clinical trials who received first-line antiretroviral therapy with Atripla (STR group) or with TDF + FTC/3TC + EFV (non-STR group) were eligible if a genotypic resistance test was available immediately after the first episode of viral failure. The DRM list from the 2013 version of IAS-USA was used.
  
  
  RESULTS
  One hundred and eighty-six patients were included in the final analysis, 122 (65.6%) from eight cohorts and 64 (34.1%) from four randomized clinical trials. The overall proportion of patients with at least one DRM at viral failure was 67.7%, including 53.4% (31 of 58) in the STR group vs. 74.2% (95 of 128) in the non-STR group (P = 0.005). Among patients exclusively from cohorts, at least one DRM was detected in 53.4% (31 of 58) in the STR group vs. 78.1% (50 of 64) in the non-STR group (P = 0.004). DRMs for individual drugs were: TDF, 15.5 vs. 16.4% (P = 0.87); 3TC/FTC, 31 vs. 35.2% (P = 0.58); and NNRTI, 51.7 vs. 65.6% (P = 0.07). The proportion of patients with an M184V/I among the 128 patients who received FTC was 32.8 vs. 36.2% among the 58 treated with 3TC (P = 0.65).
  
  
  CONCLUSIONS
  Compared to patients receiving the STR-Atripla, those receiving the same components individually in a non-STR regimen have a statistically significantly increased risk of selecting for DRMs associated with their drugs on failure.
authors.affiliation: aHospital Clinic, Barcelona, Spain bBC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, Canada cEmory University School of Medicine, Atlanta, Georgia, USA dTor Vergata University, Rome, Italy eHospital Civil de Guadalajara, University of Guadalajara, Mexico fDivision of Infectious Diseases, Department of Medicine, Stanford University gGilead Sciences, Inc., Foster City, California, USA hIrsiCaixa Foundation, Hospital Universitari Germans Trias I Pujol, Universitat Autonoma Barcelona, Spain iAntiviral Drug Monitoring Unit, INMI L Spallanzani, Rome, Italy.
authors.forename: José L
authors.initials: JL
authors.lastname: Blanco
authors.forename: Julio S G
authors.initials: JS
authors.lastname: Montaner
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Marconi
authors.forename: Maria M
authors.initials: MM
authors.lastname: Santoro
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Campos-Loza
authors.forename: Robert W
authors.initials: RW
authors.lastname: Shafer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.forename: Richard
authors.initials: R
authors.lastname: Harrigan
authors.forename: Mihn L
authors.initials: ML
authors.lastname: Nguyen
authors.forename: Carlo F
authors.initials: CF
authors.lastname: Perno
authors.forename: Lucero A
authors.initials: LA
authors.lastname: Gonzalez-Hernandez
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D017211:Treatment Failure; D014481:United States; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents