Augmented HIV vaccine trial design for estimating reduction in infectiousness and protective efficacy.

It is important to design HIV vaccine trials to estimate the efficacy of a vaccine in reducing infectiousness in addition to the protective efficacy. Currently planned phase III HIV vaccine field trials in which at-risk individuals are randomized and followed over time do not permit estimation or testing of the vaccine's effect on reducing infectiousness of vaccinees who become infected. We suggest an augmentation of these field trials that recruits steady sexual partners of the primary participants into the trial as far as they are willing to participate. This study design would allow estimation of the efficacy of the vaccine on reducing infectiousness as well as the protective efficacy. We compare the classical design that does not include partners to two different types of augmented design. In the first type of augmentation, called the non-randomized partner design, the steady sexual partners are not randomized to vaccine or placebo. In the second type of augmentation, called the randomized partner design, the steady sexual partners are also randomized to vaccine or placebo. We present a probability model based on infection status at the end of the trial that provides maximum likelihood estimates of the protective efficacy of the vaccine, VES, and the efficacy of the vaccine on reducing infectiousness, VEI. Wald statistics are used for one degree of freedom tests on VES and VEI. With the augmented design, a likelihood ratio test is used to test whether the vaccine has any effect at all. The randomized partner design has more power and provides narrower confidence intervals than does the non-randomized partner design.