Design issues in initial HIV-treatment trials: focus on ACTG A5095.

TitleDesign issues in initial HIV-treatment trials: focus on ACTG A5095.
Publication TypeJournal Article
Year of Publication2006
AuthorsRibaudo HJ, Kuritzkes DR, Schackman BR, Acosta EP, Shikuma CM, Gulick RM
JournalAntivir Ther
Volume11
Issue6
Pagination751-60
Date Published2006
ISSN1359-6535
KeywordsAnti-HIV Agents, Clinical Trials, Phase III as Topic, Double-Blind Method, Drug Therapy, Combination, HIV Infections, HIV-1, Humans, Randomized Controlled Trials as Topic, Research Design, Reverse Transcriptase Inhibitors, RNA, Viral, Sample Size, Treatment Outcome, Viral Load
Abstract

ACTG (AIDS Clinical Trials Group) A5095 was a double-blinded Phase III clinical trial designed to compare three simple strategies for the initial treatment of HIV-1 infection: a non-nucleoside reverse transcriptase inhibitor (NNRTI) combined with two nucleosides, a triple-nucleoside regimen, and an NNRTI combined with three nucleosides. The study was designed to provide a rigorous evaluation of the relative effectiveness of the three different treatment strategies in achieving and maintaining durable HIV-1 RNA suppression using both superiority and non-inferiority designs. At the same time, we sought to provide study participants with flexible treatment management options that closely reflected clinical care approaches available outside the setting of a clinical trial in this rapidly changing field of medicine. Fulfilling both of these goals required making decisions about the primary endpoint definition, blinding, treatment changes, and stopping guidelines for the primary efficacy hypotheses. In this paper we describe the study design decisions that were made, in the context of randomized HIV treatment trials in general. We hope that the discussion will inform the design of treatment strategy trials, both for HIV and for other diseases where clinical standards change rapidly. We also hope to inform the field regarding issues in choosing composite versus virological endpoints as well as other key considerations in trial design and monitoring.

Alternate JournalAntivir. Ther. (Lond.)
PubMed ID17310819
Grant ListAI 38858 / AI / NIAID NIH HHS / United States
AI 46386 / AI / NIAID NIH HHS / United States
AI 51966 / AI / NIAID NIH HHS / United States
AI27659 / AI / NIAID NIH HHS / United States
AI32775 / AI / NIAID NIH HHS / United States
M01RR00047 / RR / NCRR NIH HHS / United States
RR02635 / RR / NCRR NIH HHS / United States
U01 AI 38855 / AI / NIAID NIH HHS / United States