Abstract Nearly one quarter of the 1.1 million individuals living with HIV in the US are women, and there is a disproportionate impact on racial/ethnic minority women in the Southern US. Reproductive age women living with HIV (WLH) are highly affected by poor HIV outcomes, likely due to structural, psychosocial, and biological factors. Unfortunately, despite experiencing poor outcomes and facing unique challenges, reproductive age WLH are grossly underrepresented in HIV research. The Women's Interagency HIV Study (WIHS) is a large, comprehensive, prospective cohort study which began in 1993 and comprises almost 4,000 WLH who undergo biannual study visits with detailed structured interviews, physical and gynecologic examinations, laboratory testing, and specimen biobanking. The WIHS has 5 sites located in the South (Atlanta, Birmingham/Jackson, Chapel Hill, Miami, and Washington DC). This year, the WIHS combined with the Multicenter AIDS Cohort Study (MACS) of gay and bisexual men, to form the MACS/WIHS Combined Cohort Study (MWCCS). The Women HIV Cohort Study (WHCS) will be conducted in these 5 Southern MWCCS (previous WIHS) sites and will leverage the MWCCS structure, including access to participants, standardized assessments, specimen collections, data management, leadership committees, community advisory boards, and scientific working groups to address the following specific aims. First, we will recruit and retain 2,000 reproductive age WLH representative of the Southern epidemic into a longitudinal cohort study that will address the effects of HIV and HIV treatment in this age group. Second, we will use the scientific strength of WIHS to integrate high priority science in key thematic areas that are highly relevant for reproductive age WLH. We will provide rigorously collected sociobehavioral, clinical, and outcome data and biological specimens to scientific experts across all WIHS sites to promote multidisciplinary HIV/AIDS research. Third, we will utilize this cohort to implement unifying multidisciplinary research that is responsive to the unique health needs of reproductive age WLH. To do so, we will implement science in the area of depression, a critical mediator of health and HIV treatment outcomes of particular relevance to reproductive age WLH, and in the area of oral health. Through this science and the described plan for engagement of scientists across a broad range of relevant disciplines, the WHCS has the potential to ultimately improve the health of young WLH, optimize the gains of ART, and contribute to ending HIV across populations in the United States.