ASSESSING THE EFFECT OF HIV VACCINATION ON INFECTIOUSNESS

Traditionally, measures of vaccine efficacy have focused on a vaccine' s ability to prevent infection or disease. HIV vaccination, however, m ay have important indirect effects by reducing the level of infectious ness of vaccinees who become infected. This latter effect is not captu red by the usual estimators of vaccine efficacy. To obtain an estimate of a vaccine's effect on infectiousness, Koopman and Little have prop osed a trial design in which HIV-uninfected couples are randomized to the vaccine or control arm of the study. At least one member is assume d to be at risk of HIV infection from outside the partnership. Using t his design, we formulate martingales from counting processes which rec ord the number of infected participants over the course of the trial. An alternative estimator of a vaccine's effect on infectiousness along with an estimate of its variance is derived from these martingales. T he precision of the estimate is shown to depend on the secondary attac k rate within the couple. High secondary attack rates are required for narrow confidence intervals unless very large studies are contemplate d.