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 whic h at-risk individuals are randomized and followed over time do not per mit estimation or testing of the vaccine's effect on reducing infectio usness of vaccinees who become infected. We suggest an augmentation of these field trials that recruits steady sexual partners of the primar y participants into the trial as far as they are willing to participat e. This study design would allow estimation of the efficacy of the vac cine on reducing infectiousness as well as the protective efficacy. We compare the classical design that does not include partners to two di fferent types of augmented design. In the first type of augmentation, called the non-randomized partner design, the steady sexual partners a re not randomized to vaccine or placebo. In the second type of augment ation, called the randomized partner design, the steady sexual partner s 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 tes t whether the vaccine has any effect at all. The randomized partner de sign has more power and provides narrower confidence intervals than do es the non-randomized partner design. (C) 1998 John Wiley & Sons, Ltd.