Grant: Operating Grant - PA: HIV/AIDS Bridge Funding - Biomedical/Clinical Stream

Despite the development of several partially effective HIV prevention tools, HIV-1 continues to infect 2 million individuals per year. As these new infections disproportionally affect women the development of better female-controlled prevention options remains a global public health priority. A recent clinical trial (CAPRISA-004) demonstrated that protection by microbicides is possible, offering 39% protection for women. However this is below the threshold to make it a viable prevention option on a large scale. Improving this efficacy represents a major hurdle, as we still do not know why some individuals are infected more easily than others. To date, studies have been narrow and/or underpowered and unable to fully explain the biological basis of HIV susceptibility. The women who became infected in this large clinical trial represent the best model to understand risk factors of HIV acquisition and may provide invaluable clues on the biological processes that lead to increased risk of infection. Our preliminary data of CAPRISA-004 participants shows that specific inflammation responses in the female genital tract are associated with HIV-infection risk. Futhermore, these factors are strongly associated with the menstrual cycle and progesterone levels. We believe that hormonal contraceptives and the menstrual cycle may be responsible for these inflammation responses, and contributing to HIV infection risk. This study will determine the relationship of hormonal contraceptive use upon the immunology of the genital tract, and monitor these factors in two clinical trials in South Africa to evaluate their association with HIV infection risk. Determining this relationship and factors that underlie HIV susceptibility may have implications for both hormonal contraceptive use and the generation of new preventative technologies/vaccines against HIV.