Defining mucosal determinants of HIV risk in the CAPRISA 004 trial using high throughput proteomic approaches

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 initial research of CAPRISA-004 participants shows that mucosal factors in the genital tract may be contributing to HIV infection risk. However this picture is incomplete as mucosa contains many thousands of factors, many involved with immunity and inflammation. We have developed advanced proteomic-based methods and mathematical modeling techniques to study mucosal immune systems which can provide an unbiased global snapshot of the immune state of the mucosal environment. This 'systems biology' approach will help us to better understand the biological drivers of these responses and potentially which factors are predictors of HIV acquisition. Determining what factors made these women susceptible to HIV may give us new insight into risk factors for HIV and help lay the knowledge foundation for the development of the next generation of microbicides and/or vaccines.