HIV Vaccine Efficacy Trials: RV144 and Beyond

Despite progress in antiretroviral therapy, pre-exposure prophylaxis, microbicides, and other preventive strategies, a vaccine to prevent HIV-1 infection remains desperately needed. Development of an effective vaccine is challenged by several immunologic features of HIV-1 evidenced by the failure of five of the six HIV-1 candidate vaccine efficacy trials to date. This chapter reviews these efficacy trials with a focus on the Phase 3 RV144 trial in Thailand, the only HIV-1 vaccine efficacy trial to show a moderate protective effect of 31% with respect to placebo administration. Although modest, this protection has allowed for the study of potential immunologic correlates of protection to improve development of future HIV-1 pox-protein and other vaccine strategies. Trials in Thailand and South Africa have built upon the RV144 framework to provide additional immunologic insights which enable current and future efficacy testing of related vaccine candidates.