UNAIDS estimates 5 million new HIV infections occur every year despite widespread knowledge of the protective effects of condoms. A vaccine is not yet in sight, and the correlates of immune protection are not defined. While male circumcision appears to be 50 to 60% protective in heterosexual men, the value of this approach for rectally exposed men is not known. Oral chemoprophylaxis is a promising approach to HIV prevention with proven precedent in other infectious diseases. A prevention trial titled """"""""Chemoprophylaxis for HIV Prevention in Men"""""""" was funded in August 2005 as U01-AI064002. The clinical trial will evaluate the efficacy and safety of the most promising candidate identified in pre-clinical studies: co-formulated emtricitabine 200 mg / tenofovir disoproxl fumarate 300 mg (FTC/TDF). In the first 16 months of this project, the protocol, procedures, and instruments have been fully developed based on extensive global and local consultations with vulnerable communities, medical experts, government officials, and other interested parties. The protocol has now been approved by the NIH, the US FDA, ethical committees in San Francisco, Peru and Ecuador, and the Ecuadorian Ministry of Health. Protocol changes for increasing protections for research participants have increased total project costs, for which supplemental funds are now requested. The final project will enroll 1400 men who will be randomized 1:1 to receive daily oral FTC/TDF versus placebo and followed for up to 96 weeks for seroconversion (aim 1), adverse events (aim 2), HBV interactions (aim 3), bone and fat effects (aim 4), seroconverter outcomes (aim 5), and risk behavior (aim 6). Study sites are selected that have the highest incidence of HIV-1 infection in recent surveys and trials, have the required infrastructure for Good Clinical Practices, and represent extensive human genetic and cultural diversity. The sample size is sufficient to detect cost-effective levels of HIV-1 prevention as a proof of concept. The focus on men in this study complements clinical trials in women in Asia and Africa. The safety and efficacy of Chemoprophylaxis may differ in men and women due to differences in reproductive biology, the mucosal surfaces that are typically exposed to HIV, behavioral differences, and pharmacokinetics. This research ultimately aims to break the epidemic cycle of HIV-1 by protecting men at risk for HIV, and may spare their female sexual partners and their future children. ? ? ?
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