What constitutes efficacy for a human immunodeficiency virus vaccine that ameliorates viremia: issues involving surrogate end points in phase 3 trials.

TitleWhat constitutes efficacy for a human immunodeficiency virus vaccine that ameliorates viremia: issues involving surrogate end points in phase 3 trials.
Publication TypeJournal Article
Year of Publication2003
AuthorsGilbert PB, DeGruttola VG, Hudgens MG, Self SG, Hammer SM, Corey L
JournalJ Infect Dis
Volume188
Issue2
Pagination179-93
Date Published2003 Jul 15
ISSN0022-1899
KeywordsAIDS Vaccines, Biomarkers, Clinical Trials, Phase III as Topic, Decision Making, Disease Progression, HIV, HIV Infections, Humans, Licensure, Treatment Outcome, Viral Load, Viremia
Abstract

Initial human immunodeficiency virus (HIV) vaccines are unlikely to prevent acquisition of HIV in all recipients. Moreover, several HIV vaccines are under evaluation that are designed to reduce viremia after acquisition of infection. Such vaccines could provide important benefits to delay HIV progression and to reduce transmission. The decision to license a vaccine on the basis of observed effects on virus load and other postinfection surrogate end points in an efficacy trial is complicated by uncertainty about whether the vaccine effects will persist and reliably predict clinical effects, and by the challenge in interpreting the data posed by treatment of some seroconverters with antiretroviral drugs. Here, we evaluate how analyses of certain surrogate end points can be used for inferring clinically significant vaccine effects and propose end points that could be evaluated in efficacy trials to support licensure. The assessment suggests that a vaccine demonstrating moderately durable effects to delay therapy and to ameliorate viremia merits consideration for licensure.

DOI10.1086/376449
Alternate JournalJ. Infect. Dis.
PubMed ID12854072
Grant ListAI 24643 / AI / NIAID NIH HHS / United States
AI 42848 / AI / NIAID NIH HHS / United States
AI 45206 / AI / NIAID NIH HHS / United States
AI 46386 / AI / NIAID NIH HHS / United States
AI 46703 / AI / NIAID NIH HHS / United States
AI 48013 / AI / NIAID NIH HHS / United States
AI 51164 / AI / NIAID NIH HHS / United States
AI 54165-01 / AI / NIAID NIH HHS / United States