Grant: Team Grant: HIV/AIDS Biomedical and Clinical Research - Prevention - Focused

The number of new HIV infections each year continues to remain unacceptably high. Just as cancer therapy attacks with multiple drugs, we will employ a combination of biomedical approaches that blocks HIV infections in different ways. Firstly, will be to use anti-HIV drugs that work by blocking the ability of the virus to replicate. Secondly, will be to block the inflammatory process that brings the cells that HIV primarily infects into the genital tract using anti-inflammatory drugs. Based on research pioneered by our team members, we have shown that inflammation greatly increases the risk of HIV transmission and can actually nullify the effects of anti-HIV drugs to prevent infections. A pilot study we performed shows that using the anti-inflammatory drug acetylsalicylic acid (ASA or aspirin) reduces by 35% the number of HIV target cells in the genital tract. We will conduct studies with immediate, mid-term and long-term goals. For the immediate impact studies, we will work with a cohort of female sex workers in Nairobi, Kenya who are highly exposed to HIV and are using anti-HIV drugs for prevention. We will place women with high levels of genital inflammation on the anti-inflammatory drug ASA to assess if the number of HIV target cells in the genital tract is reduced. Our mid-term studies will use a laboratory mouse with a human immune system to determine the mechanism of how ASA affects the migration of HIV target cells and we perform HIV infection studies to directly test is ASA can reduce HIV infection. Finally, because taking drug daily can be challenging for some people, we will assess in the humanized mouse model, the long-term goal of using an intravaginal ring that would deliver a contraceptive, an anti-HIV drug and an anti-inflammatory drug. This proposal will determine if our "Combination HIV Prevention" approach is more effective thereby providing women with more options for protecting themselves.