Advances in human clinical trials of vaccines to prevent HIV/AIDS and other HIV prevention interventions.

Nearly three decades after the first description in 1981 of the syndrome eventually designated as AIDS, only five efficacy trials testing just three HIV vaccine concepts have been initiated. In 2007, an efficacy analysis was conducted for the first of a newer generation of candidate HIV/AIDS vaccines based entirely on cellular immunity. Data from this study, known as the Step Study, indicated that the vaccine neither protected against infection nor lowered viral loads after infection. Furthermore, certain vaccinees were at higher risk of HIV infection following vaccination. This article explores these disappointing and surprising outcomes, reviews earlier efficacy studies and more recent discovery research, and provides a critical analysis of the field. Other HIV prevention interventions are considered because their successful implementation may dramatically alter the milieu for future HIV vaccine field trials, particularly impacting study designs and increasing sample sizes if incidence falls.