Background: HIV prevention research has been fraught with ethical concerns since its inception. These concerns were highlighted during HIV vaccine research and have been elaborated in microbicide research. A host of unique ethical concerns pervade the microbicide research process from trial design to post-trial microbicide availability. Given the urgency of research and development in the face of the devastating HIV pandemic, these ethical concerns represent an enormous challenge for investigators, sponsors and Research Ethics Committees (RECs) both locally and internationally.
Discussion: Ethical concerns relating to safety in microbicide research are a major international concern. However, in the urgency to develop a medically efficacious microbicide, some of these concerns may not have been anticipated. In the risk-benefit assessment of research protocols, both medical and psycho-social risk must be considered. In this paper four main areas that have a potential for medical and/or psycho-social harm are examined. Male partner involvement is controversial in the setting of covert use of microbicides. However, given the long-term exposure of men to experimental products, this may be methodologically, ethically and legally important. Covert use of microbicides may impact negatively on relationship dynamics leading to psychosocial harm to varying extents. The unexpectedly high rates of pregnancy during clinical trials raise important methodological and ethical concerns. Enrollment of adolescents without parental consent generates ethical and legal concerns that must be carefully considered by RECs and trial sites. Finally, paradoxical outcomes in recent trials internationally have advanced the debate on the nature of informed consent and responsibility of researchers to participants who become HIV positive during or after trials.
Summary: Phase 3 microbicide trials are an undisputed research and ethical priority in developing countries. However, such trials must be conducted with attention to both methodological and ethical detail. It is imperative that guidelines are formulated to ensure that high ethical standards are maintained despite the scientific urgency of microbicide development. Given the controversy raised by emergent ethical issues during the course of microbicide development, it is important that international consensus is reached amongst the various ethics and regulatory agencies in developing and developed countries alike.