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.
*Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham, AL
†School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
‡Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA
§Division of Infectious Diseases, Weill Medical College of Cornell University, New York, NY
‖Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, PA
¶Division of Infectious Diseases University of California, San Diego, CA
#Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC
**INSERM U943, Paris, F-75 013, France; UPMC Univ Paris 06, UMR_S 943, Paris, F-75013 France; AP-HP, Hôpital Avicenne, Service des maladies infectieuses et tropicales, Bobigny, F-93 000 France
††UCL Medical School, London, United Kingdom
‡‡Health Protection Agency, Colindale, London, United Kingdom
§§Division of Infectious Diseases, University of Calgary, Calgary, Canada
‖‖Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
¶¶Division of Epidemiology and Population Health, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada; and Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada
##Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
***INSERM, U897, University Bordeaux Segalen, Bordeaux, France
†††Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, University of Milan, Milan, Italy
‡‡‡HIV Atlanta VA Cohort Study, Atlanta Veterans Affairs Medical Center, Decatur, GA
§§§Division of Infectious Diseases, Hospital Son Dureta, Palma de Mallorca, Spain
‖‖‖Infectious Diseases Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
¶¶¶First Department of Internal Medicine, University of Köln, Köln, Germany
###Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Av Sant Antoni Maria Claret, Barcelona, Spain
****Department of Medicine, Division of Infectious Diseases, University of Washington, Washington, DC
The ACTG is supported by grant AI-68636 from the US National Institutes of Health, with additional support provided by grant K23MH082641 (MJM), U01AI068634 (HJR), and K24AI-51966 (RMG). The ART Cohort Collaboration is supported by the UK Medical Research Council grant G0700820. Sources of funding of individual cohorts include the Agence Nationale de Recherche contre le SIDA, the Institut National de la Santé et de la Recherche Médicale (INSERM), the French, Italian, Spanish and Swiss Ministries of Health, The Swiss HIV Cohort Study (SHCS), supported by the Swiss National Science Foundation (Grant No. 33CSC0- 08787) and by the SHCS research foundation, the Stichting HIV Monitoring, the European Commission, the British Columbia and Alberta Governments, the Michael Smith Foundation for Health Research, the Canadian Institutes of Health Research, the VHA Office of Research and Development and unrestricted grants from GlaxoSmithKline, Roche and Boehringer-Ingelheim. Supported in part by the “Spanish Network for AIDS Research (RIS; ISCIII-RETIC RD06/006).
M.J.M. has received consulting fees (advisory board) from Bristol-Myers Squibb, Gilead Sciences, and Merck Foundation; and grant support from Bristol-Myers Squibb, Pfizer, Inc, Tibotec Therapeutics, and Definicare, LLC; R.M.G. has received consulting fees from Bristol-Myers, Gilead, Merck, Tibotec, ViiV and Virostatics and research grant support (to Weill Cornell Medical College) from Merck, Pfizer, Tibotec, and ViiV; Sophie Abgrall has received support for conference attendance from pharmaceutical companies including Glaxo-SmithKline, Abbott, Tibotec, Gilead and Boehringer Ingelheim; M.J.G. has received consulting fees (advisory boards) from Abbott, Bristol-Myers Squibb, Viiv Healthcare, Janssen, Merck and Gilead and has had grant support from Gilead, ViiV Healthcare and Pfizer; H.F.G. has been an adviser and/or consultant for GlaxoSmithKline, Abbott, Novartis, Boehringer Ingelheim, Roche, Tibotec, and Bristol-Myers Squibb and has received unrestricted research and educational grants from Roche, Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Tibotec, and Merck Sharp and Dohme (MSD) (all money went to institution); G.C. has received consulting fees (Scientific Committee) from Roche, and has had scientific responsibilities in projects receiving specific grant support from Gilead, Tibotec, Boehringer Ingelheim, GlaxoSmithKline, Roche, Pfizer, MSD, Bristol-Myers Squibb, Janssen, ViiV Healthcare, and managed through her Institution or a nonprofit society; C.S. has received consulting fees from Bristol-Myers Squibb, Gilead Sciences, Tibotec, Glaxo Smith Kline, Abbott and Roche and grant support from Bristol-Myers Squibb and Glaxo Smith Kline; C.W. has received consulting fees from Boehringer Ingelheim, fees for speaking engagments from Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, MSD, Janssen-Cilag, Essex, Pfizer and Abbott; P.D. has received consulting fees (advisory board) from Bristol-Myers Squibb, Gilead Sciences, Boehringer Ingelheim, Merck, Abbott, Janssen & Cilag, ViiV healthcare and Theratechnologies and grant support from Abbott, Boehringer Ingelheim, Pfizer, Inc, and Tibotec Therapeutics; M.S.S. has received consulting fees from Ardea Biosciences, Avexa, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Monogram Biosciences, Pain Therapeutics, Panacos, Pfizer, Progenics, Roche Laboratories, Tibotec, Tobira Therapeutics, and Vicro and research support from Achillion Pharmaceuticals, Avexa, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Panacos, Pfizer, Progenics, Theratechnologies and Tibotec. All remaining authors have no conflicts of interest to declare.
The members of the ACTG 5095 and 5142 study team and their support are listed in Appendix 1.
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Correspondence to: Michael J. Mugavero, MD, MHSc, CCB 142, 908, 20th Street South, Birmingham, AL 35294-2050 (e-mail: email@example.com).
Received April 27, 2011
Accepted July 28, 2011