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, may have important indirect effects by reducing the level of infectiousness of vaccinees who become infected. This latter effect is not captured by the usual estimators of vaccine efficacy. To obtain an estimate of a vaccine's effect on infectiousness, Koopman and Little have proposed a trial design in which HIV-uninfected couples are randomized to the vaccine or control arm of the study. At least one member is assumed to be at risk of HIV infection from outside the partnership. Using this design, we formulate martingales from counting processes which record 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. The precision of the estimate is shown to depend on the secondary attack rate within the couple. High secondary attack rates are required for narrow confidence intervals unless very large studies are contemplated.