Comparative effectiveness of initial antiretroviral therapy regimens: ACTG 5095 and 5142 clinical trials relative to ART-CC cohort study.

TitleComparative effectiveness of initial antiretroviral therapy regimens: ACTG 5095 and 5142 clinical trials relative to ART-CC cohort study.
Publication TypeJournal Article
Year of Publication2011
AuthorsMugavero MJ, May M, Ribaudo HJ, Gulick RM, Riddler SA, Haubrich R, Napravnik S, Abgrall S, Phillips A, Harris R, M Gill J, de Wolf F, Hogg R, Günthard HF, Chêne G, Monforte AD'Arminio, Guest JL, Smith C, Murillas J, Berenguer J, Wyen C, Domingo P, Kitahata MM, Sterne JAC, Saag MS
Corporate AuthorsAIDS Clinical Trial Group DACS 241 Team, AIDS Clinical Trial Group Study 5095 Team, AIDS Clinical Trial Group Study 5142 team, Antiretroviral Cohort Collaboration
JournalJ Acquir Immune Defic Syndr
Volume58
Issue3
Pagination253-60
Date Published2011 Nov 1
ISSN1944-7884
KeywordsAdolescent, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Cohort Studies, Double-Blind Method, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Treatment Outcome, Young Adult
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.

DOI10.1097/QAI.0b013e318230372e
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID21857357
PubMed Central IDPMC3196673
Grant ListAI-68636 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
G0700820 / / Medical Research Council / United Kingdom
K23 MH082641 / MH / NIMH NIH HHS / United States
K23 MH082641-04 / MH / NIMH NIH HHS / United States
K23MH082641 / MH / NIMH NIH HHS / United States
K24 AI051966 / AI / NIAID NIH HHS / United States
K24 AI064086 / AI / NIAID NIH HHS / United States
K24 AI064086-06 / AI / NIAID NIH HHS / United States
K24AI-51966 / AI / NIAID NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
U01 AI027670 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068634-05 / AI / NIAID NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States
U01AI068634 / AI / NIAID NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada