STATISTICAL ISSUES IN THE DESIGN OF HIV VACCINE TRIALS

HIV vaccine trials present significant challenges related to trial end points, vaccine efficacy measurement, and the role of nonvaccine inter ventions. Infection is a valid endpoint for detecting sterilizing immu nity. But if the vaccine prevents AIDS without preventing infection, i nfection may be a misleading surrogate. Appropriate endpoints must be defined for other mechanisms of vaccine action. Direct, indirect, beha vioral, and biological effects all determine vaccine efficacy. False s ecurity among HIV-vaccine recipients may make negative behavioral effe cts an important component of vaccine performance. Both biological pot ency and a more comprehensive program effectiveness should be measured . These goals may require unblinded designs or community randomization . Nonvaccine interventions are currently the only HIV-prevention strat egy. Support for larger scale implementation requires more rigorous ev aluation that is less dependent on self-reported behavioral changes. T he vaccine trial cohorts provide a unique opportunity to cost-effectiv ely evaluate behavioral interventions.