Assessing HIV vaccine effects.

It is unlikely that human immunodeficiency virus (HIV) vaccines will create impenetrable barriers to infection. When the barriers to infection are broken, however, vaccine effects on the progression of infection to disease and on the contagiousness of infection could be considerable. The usual outcomes of vaccine trials are either infection or disease. The authors argue that for HIV vaccines, the alternative outcome of contagiousness may be more important. Because of the long incubation period to acquired immunodeficiency syndrome (AIDS), a vaccine trial with AIDS as the outcome would be a long and costly undertaking. Because contagiousness is concentrated into the period of primary infection, vaccine trials assessing contagiousness would not take as long. An approach to assessing vaccine effects on the contagiousness of primary infection while simultaneously assessing protection against infection is presented. It involves randomizing vaccination of couples in whom both individuals are uninfected and one or both have a risk of infection outside the couple. In such a study, the vaccine effect on susceptibility to infection can be estimated from the proportions of vaccinated and unvaccinated couples in whom neither partner is infected. Estimation of the contagiousness effect also uses information on the frequency with which both partners are infected. In areas of the world where heterosexual epidemics are emerging within the context of concurrent partnerships, the randomization of vaccination of couples could increase the efficiency and decrease the costs of vaccine trials.