The overall goal of the proposed research is to improve the evaluation of vaccine efficacy and effectiveness in the field.
The specific aims of this application are to develop feasible designs and statistical procedures for Phase III HIV vaccine trials so as to estimate three different vaccine effects: vaccine efficacy for susceptibility to infection (VES); vaccine efficacy for reduction in infectiousness of infected vaccinated persons (VEI); and vaccine efficacy for reduction in illness progression in HIV infected persons (VEP). The researchers will also consider estimating the waning of such effects. Suggested trial designs will be based on the enrollment of uninfected primary participants who will be randomized to vaccine or placebo and followed prospectively. To estimate VEI, the researchers will augment the trials by recruiting sexual partners of primary participants prospectively or locating recent sexual partners of vaccine trial participants who have become infected, and then develop statistical methods for these study designs. To estimate VEP the researchers will compare surrogate marker information, such as plasma RNA or DNA levels or CD4 counts of infected vaccinated persons, to that for infected unvaccinated persons. The researchers will adapt the designs to the realities of the vaccine trials being planned in Thailand and Brazil. Finally, they will use simulations to generate data similar to those expected in different designs of HIV vaccine trials to test the statistical methods.
