Women's Interagency HIV Study (WIHS-V)

DESCRIPTION (provided by applicant): 2011 was a transformative year in HIV research, providing evidence and raising hope that the HIV epidemic globally can potentially be not only controlled but also effectively aborted in our lifetime through both prevention and cure. Effective primary prevention through microbicides, pre-exposure prophylaxis and treatment of persons living with HIV (PLWH) seems within our reach. Equally important, basic science advances suggest that cure is possible through activation and/or elimination of HIV proviral DNA from host cells. We propose a WIHS scientific agenda that informs these possible routes to defeating HIV, through investigations of genital tract innate immune factors protecting against HIV-infection; identification of epigenetic changes in the provirus that may define a target for cure; and elucidating cell-to-cell viral transfer. We will continue to use WIHS's robust database to inform effective treatment for women and persons of African descent. Of the 34.0 million PLWH globally more than half of are women, and more than 75% are of African ancestry; nearly all studies of the efficacy of antiretroviral therapy (ART) are in men of European descent. Thus, epidemiologic and translational investigation of population- based effectiveness of ART in WIHS, which is 100% women and >60% of African descent, will provide critical information for patients and providers both in the US and globally. Further, with 18 years of prospective data collection the WIHS is able to investigate clinical manifestations in aging populations, including studies of changes in the genital tract with reproductive aging. The Bronx WIHS has provided both operational excellence and scientific leadership nationally since WIHS's inception in 1993. In WIHS V we will continue to lead the WIHS-wide investigations in HPV and cervical neoplasia; cardiovascular disease and inflammation; genital tract mucosal immunology and virology; immunogenetics; HIV virology; musculoskeletal manifestations of HIV disease; and host characteristics influencing population based effectiveness of ART. We will also continue our excellent operational performance in providing high volume, complete, high quality data both for the WIHS core activities, and all substudies.