A preventive vaccine against HIV-1 would be a valuable tool in curbing the pandemic. Evaluation of vaccine candidates in the SIV non-human primate model is an important step in the assessment of the potential efficacy of analogous HIV-1 vaccines [1
]. Historically, vaccine regimens have been tested in non-human primates by administering a single high dose intravenous or mucosal inoculation of the challenge virus, typically resulting in infection of all animals under study after one exposure. Recently, evaluation of candidate HIV vaccines (and other preventive interventions) has entailed repeated low-dose mucosal challenge studies [3
] that may more closely mimic typical exposure in natural human transmission settings. A primary objective of these studies is to assess vaccine efficacy for prevention of infection.
Since the repeated low-dose challenge study design has only recently been implemented in evaluation of candidate HIV vaccines, the literature on design considerations of these studies is limited. Recent investigations [7
] demonstrated such challenge studies can be adequately powered to test for vaccine efficacy to prevent infection with feasible samples sizes of non-human primates. However, the effect of various design parameters such as the challenge dose, the percent of animals susceptible to infection, or the unequal allocation of animals to vaccine and placebo arms have not been systematically investigated. Given results from a recent HIV vaccine efficacy trial [9
], the possibility that vaccination may increase the probability of infection needs to be entertained. Direct comparisons of different statistical tests employed in the analysis of repeated low-dose challenge studies are also needed.
In this paper, we describe simulation studies which were conducted to better understand how the design of challenge experiments can affect the statistical power to detect a candidate vaccine’s effect. Simulated scenarios were varied according to the total sample size, the per-exposure risk of infection in controls, the magnitude and direction of the vaccine effect, the fraction allocated to vaccine or control, the proportion of susceptible animals, and the maximum number of challenges per animal. While this work is motivated by the development of an HIV vaccine, our results can be used to inform the design of challenge studies for evaluation of other vaccines and other preventive interventions.