Challenges in microbicide trial design and implementation.

Microbicide development began more than fifteen years ago, when optimism about the swift development of an HIV vaccine began to wane, and researchers recognized that significant progress in HIV transmission prevention could not be expected with the currently available HIVprevention tools (van de Wijgert and Coggins 2002). Sexual abstinence and limiting the number of sexual partners may not be feasible for those women who, because of their constrained educational and employment opportunities, are financially dependent on men. After two decades of male condom promotion, the absolute number of male condoms used worldwide has increased dramatically, but consistent condom use in primary partnerships remains rare. Women are often unable to convince their male partners to use a condom, or to remain with one partner, because of social, cultural, and economic gender inequalities. Microbicides are being developed as products to apply topically inside the vagina or rectum to prevent infection with HIV and, potentially, with other sexually transmitted infections (STIs). They could be formulated as gels, creams, suppositories, or vaginal rings; they could be contraceptive or not; and they could be used alone or in combination with a physical barrier. For many women and couples, the importance of having children is a major obstacle to condom use, and noncontraceptive microbicides would offer them a means of protecting themselves from HIV while trying to conceive. By reducing the risk of HIV infection among women, microbicides could contribute to a reduction in mother-to-child transmission. They could prevent transmission from women to their male partners, and reinfection among women who are HIV-positive. Researchers are also investigating ways that microbicides can be formulated for use in the rectum during anal sex. Remarkable progress has been made in the microbicides field in recent years. According to the Alliance for Microbicide Development, 29 candidate products are in the pipeline (AMD 2006). The majority of these are in preclinical stages of development, approximately ten are in Phase I and II safety trials, and five are in Phase IIb/III effectiveness trials. Funding for microbicide development increased significantly (Harrison et al. 2005), and the global movement for microbicides continues to grow, uniting women’s health and AIDS advocates, researchers, governments, and institutions. A biennial international microbicides conference was established in 2000, and attendance has grown steadily with each subsequent meeting. As candidate products are moving from the laboratory to human communities, many challenges in microbicide trial design and implementation have surfaced. Some of these challenges are scientific in nature, but others are ethical, political, or logistical. In this Commentary, we highlight some of the challenges that we have encountered while establishing microbicide trial sites and in designing and implementing microbicide trials in Africa and Asia.