Rates of Disease Progression according to Initial Highly Active Antiretroviral Therapy Regimen: A Collaborative Analysis of 12 Prospective Cohort Studies
Background.
No large clinical end‐point trials have been conducted comparing regimens among human immunodeficiency virus type 1–positive persons starting antiretroviral therapy. We examined clinical progression according to initial regimen in the Antiretroviral Therapy Cohort Collaboration, which is based on 12 European and North American cohort studies.
Methods.We analyzed progression to death from any cause and to AIDS or death (AIDS/death), comparing efavirenz (EFV), nevirapine (NVP), nelfinavir, idinavir, ritonavir (RTV), RTV‐boosted protease inhibitors (PIs), saquinavir, and abacavir. We also compared nucleoside reverse‐transcriptase inhibitor pairs: zidovudine/lamivudine (AZT/3TC), stavudine (D4T)/3TC, D4T/didanosine (DDI), and others.
Results.A total of 17,666 treatment‐naive patients, 55,622 person‐years at risk, 1617 new AIDS events, and 895 deaths were analyzed. Compared with EFV, the adjusted hazard ratio (HR) for AIDS/death was 1.28 (95% confidence interval [CI], 1.03–1.60) for NVP, 1.31 (95% CI, 1.01–1.71) for RTV, and 1.45 (95% CI, 1.15–1.81) for RTV‐boosted PIs. For death, the adjusted HR for NVP was 1.65 (95% CI, 1.16–2.36). The adjusted HR for death for D4T/3TC was 1.35 (95% CI, 1.14–1.59), compared with AZT/3TC.
Conclusions.Outcomes may vary across initial regimens. Results are observational and may have been affected by bias due to unmeasured or residual confounding. There is a need for large, randomized, clinical end‐point trials.
Received 28 November 2005; accepted 27 February 2006; electronically published 31 July 2006.
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(See the editorial commentary by Hughes, on pages 542–4.)
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Presented in part: 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, 24–27 July 2005 (abstract MoDe0301).
Potential conflicts of interest: A.N.P. has received travel grants, grants, consultancy fees, and honoraria from various pharmaceutical companies, including Roche, DuPont, Bristol‐Myers Squibb (BMS), Boehringer Ingelheim (BI), and GlaxoSmithKline (GSK). M.E. has received travel grants, grants, or honoraria from BMS, BI, and GSK. B.L. has received travel grants from Roche, Abbott, BMS, GSK, Merck Sharp and Dohme, and Aventis. C.A.S. has received honoraria, consultancy fees, and travel grants from a number of pharmaceutical companies, including Roche, BMS, BI, Gilead Sciences, and GSK. M.M. and J.A.C.S. have received travel grants from GSK. G.F. is an employee of GSK. D.C. has received travel grants, consultancy fees, and honoraria from various pharmaceutical companies, including Abbott, GSK, BMS, Gilead, Roche, and BI.
Financial support: UK Medical Research Council (grant RD1564 to the Antiretroviral Therapy Cohort Collaboration). 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; the French, Italian, and Swiss Ministries of Health; Stichting HIV Monitoring; the European Commission; the governments of British Columbia and Alberta; the Michael Smith Foundation for Health Research; the Canadian Institutes of Health Research; and GlaxoSmithKline, Roche, and Boehringer Ingelheim (unrestricted grants).
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Analysis and writing committee members are listed at the end of the text, and a complete list of study group members is given in the Appendix, which is not available in the print edition of the Journal.