It cannot always be assumed that the outcome will be the same in different groups; efficacy may differ depending on the route of viral exposure owing to differences in transmission efficiency, drug penetration into tissues, or the types of cells that are first exposed to virus. Body size differs widely and directly affects drug levels that may impinge on efficacy and side effects. Other variables may be gender, genetics, adherence, gray and black markets for drugs, access to safe storage, and social circumstances. Performing prevention research only in Paris, San Francisco, or New York would be a tragic mistake that would perpetuate the situation of antiretroviral therapy, which has been optimized for the richest 2% of those infected. Involvement of community members and leaders is a proven way to protect vulnerable persons who participate in research. Community advisory boards, community consultations, and independent, local, ethical review boards are well-established mechanisms for fostering community input into research design and implementation. They help to assure that studies provide benefit to study populations, while minimizing risks to individuals, and that there are procedures to obtain and maintain genuine informed consent. Community advisory boards and ethical review boards also address issues that emerge during the trial, including unexpected or serious adverse events, participant complaints, public misperceptions and rumors, and media communications. Access to ombudsmen for participants is warranted and is already provided by some ethical review boards. Local community advisers and ethical review boards should be involved in deliberations early in the development of research projects before sponsors’ final approval is sought.

PrEP research was first proposed in 2001, before the advent of a global response for providing antiretroviral therapy (4). Some treatment advocates were angry that participants found to be HIV-infected before or during the trials might not have access to therapy and that antiretroviral drugs might be diverted from life-saving treatment programs. Since 2001, several agencies have been funding antiretroviral therapy on a massive scale. Clinics have opened, or are under development, at all PrEP trial sites, thereby providing access to antiretroviral therapy in these communities. Community expectations for access to treatment should prompt good-will efforts but should not create ethical obligations that would block prevention research in