Simulations to evaluate HIV vaccine trial designs

Many HIV vaccine trials have been proposed to evaluate susceptibility of individuals. However, vaccines may also affect an epidemic's course at the population level by altering the infectiousness of vaccinated individuals who become infected. A vaccine trial design that does not estimate both susceptibility and infectiousness might reject a proposed vaccine that is capable of halting the HIV epidemic. We describe a vaccine trial design called the Retrospective Partner Trial (RPT), which can quantify vaccine effects on both susceptibility and infectiousness. We describe HIVSIM, a simulation environment that generates simulated populations and allows for empirical evaluation of the statistical power of the RPT. HIVSIM explicitly models a number of factors which influence transmission and prevalence, and which have proven difficult to model using standard models. These factors include the infection stage of infected, individuals, partnership selection, the duration of partnerships and concurrence, and transmission of HIV. The simulation analysis indicates that the RPT design has substantially greater statistical power for identifying vaccines which, in spite of exhibiting poor protection against infection, are nonetheless capable of halting the HIV epidemic by substantially reducing the infectiousness of vaccinated individuals who become infected.