title: Comparative effectiveness of initial antiretroviral therapy regimens: ACTG 5095 and 5142 clinical trials relative to ART-CC cohort study.
abstract: BACKGROUND
  The generalizability of antiretroviral therapy (ART) clinical trial efficacy findings to routine care settings is not well studied. We compared the relative effectiveness of initial ART regimens estimated in AIDS Clinical Trial Group (ACTG) randomized controlled trials with that among patients receiving ART at Antiretroviral Therapy Cohort Collaboration (ART-CC) study sites.
  
  
  METHODS
  Treatment-naive HIV-infected patients initiating identical ART regimens in ACTG trials (A5095 and A5142) and at 15 ART-CC cohort study sites were included. Virological failure (HIV-1 RNA >200 copies/mL) at 24 and 48 weeks, incident AIDS-defining events and mortality were measured according to study design (ART-CC cohort vs. ACTG trial) and stratified by third drug [abacavir (ABC), efavirenz (EFV), and lopinavir/r (LPV/r)]. We used logistic regression to estimate and compare odds ratios (OR) for virological failure between different regimens and study designs, and used Cox models to estimate and compare hazard ratios for AIDS and death.
  
  
  RESULTS
  Compared with patients receiving ABC, those receiving EFV had roughly half the odds of 24-week virologic failure (>200 copies/mL) in both ACTG 5095 (OR = 0.53, 95% confidence interval: 0.36 to 0.79) and ART-CC (0.46, 0.37 to 0.57). Virologic superiority of EFV (vs. ABC) seemed comparable in ART-CC and ACTG 5095 (ratio of ORs 0.86, 95% confidence interval: 0.54 to 1.35). Odds ratios for 48-week virologic failure, comparing EFV with LPV/r, were also comparable in ACTG 5142 and ART-CC (ratio of ORs: 0.87, 0.45 to 1.69).
  
  
  CONCLUSIONS
  Between ART regimen virologic efficacy of third drugs ABC, EFV, and LPV/r observed in the ACTG 5095 and 5142 trials seem generalizable to the routine care setting of ART-CC clinical cohorts.
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham, AL, USA. mmugavero@uab.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mugavero
authors.forename: Margaret
authors.initials: M
authors.lastname: May
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Riddler
authors.forename: Richard
authors.initials: R
authors.lastname: Haubrich
authors.forename: Sonia
authors.initials: S
authors.lastname: Napravnik
authors.forename: Sophie
authors.initials: S
authors.lastname: Abgrall
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.forename: Ross
authors.initials: R
authors.lastname: Harris
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Robert
authors.initials: R
authors.lastname: Hogg
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.forename: Antonella
authors.initials: A
authors.lastname: D'Arminio Monforte
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Guest
authors.forename: Colette
authors.initials: C
authors.lastname: Smith
authors.forename: Javier
authors.initials: J
authors.lastname: Murillas
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Christoph
authors.initials: C
authors.lastname: Wyen
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Mari M
authors.initials: MM
authors.lastname: Kitahata
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents