Abstract Over 250,000 women in the United States are living with HIV, but limited research has addressed the physical and mental health outcomes among younger women living with HIV (WLHIV). Because health status in the reproductive years and surrounding pregnancy critically affects lifelong health, understanding health outcomes among young WLHIV of reproductive age before, during, and after pregnancy is of substantial public health importance in the US and worldwide. The maternal outcomes of WLHIV are inextricably linked to the long-term health and survival of their children. The Pediatric HIV/AIDS Cohort Study (PHACS), conducted at 21 sites across the US and Puerto Rico, has been following young WLHIV of reproductive age and their children since 2007, with over 2000 birth mothers and >2800 HIV-exposed uninfected (HEU) children. Mothers with perinatally acquired HIV (PHIV) are of specific interest, and the PHACS network includes >400 such women with PHIV (WPHIV) along with their 251 HEU children. Utilizing the successful and longstanding PHACS research infrastructure and existing cohorts, we will establish the Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) cohort, a cohort of 2000 pregnant, non-pregnant or nulliparous WLHIV of reproductive age from geographically diverse, high HIV prevalence areas. Leveraging PHACS, cost-effective and targeted enrollment and follow-up for longitudinal data collection will be achieved; we will also establish a rich biorepository which links WLHIV to their children’s data and biospecimens. Thus, the HOPE research platform will support high impact scientific studies central to the health of young WLHIV. Our scientific aims for the HOPE cohort are: (1) to evaluate the effects of HIV-related disease and treatment factors on reproductive health, non-communicable diseases, and oral health of WLHIV as well as psychosocial determinants of these health outcomes (engagement in care, mental health diagnoses, racism, inequity and stigma, disclosure of HIV, and substance use/misuse), and (2) To assess child health outcomes and their impact on the health of WLHIV, including maternal HIV disease progression, antiretroviral therapy (ART) adherence, engagement in care and maternal mental health. Overall, HOPE will create a platform to explore the multilevel determinants and mechanisms that influence the short and longer-term health of WLHIV during their reproductive years, as well as the health of their children, and will serve as a resource for future multidisciplinary studies in areas such as genetics and epigenetics, microbiome/virome/proteomes and immune activation, to provide better understanding of potential inflammatory and epigenetic processes associated with these outcomes.