Exposure efficacy and change in contact rates in evaluating prophylactic HIV vaccines in the field

Field studies of the efficacy of prophylactic vaccines in reducing susceptibility rely on the assumption of equal exposure to infection in the vaccinated and unvaccinated groups. Differential exposure to infection could, however, be the goal of other types of intervention programme, or it could occur secondary to belief in the protective effects of a prophylactic measure, such as vaccination. We call this differential exposure the exposure efficacy, or behaviour efficacy. To study the relative contribution of unequal exposure to infection and differential susceptibility to the estimate of vaccine efficacy, we formulate a simple model that explicitly includes both susceptibility and exposure to infection. We illustrate this on the example of randomized field trials of prophylactic human immunodeficiency virus vaccines. Increased exposure to infection in the vaccinated group may bias the estimated reduction in susceptibility. The bias in the estimate depends on the choice of efficacy parameter, the amount of information used in the analysis, the distribution and level of protection in the population, and the imbalance in exposure to infection. Sufficient increase in contacts in the vaccinated could result in the vaccine being interpreted as having an immunosuppressive effect. Estimates of vaccine efficacy are generally more robust to imbalances in exposure to infection when the detailed history of exposure to infection can be used in the analysis or at high levels of protection. The bias also depends on the relationship between the distribution of vaccine protection and the distribution of behaviour change, which could differ between blinded and unblinded trials.