Pediatric HIV/AIDS Cohort Study (PHACS): Research on Immune Aging, Supporting Reproductive Health, and Perinatal Acquisition: Elucidating Relationships in HIV (RISE) - PROJECT SUMMARY People with HIV (PWH) experience a substantial burden of adverse reproductive and sexual health outcomes, perpetuated by psychosocial stress, chronic inflammation, lifelong exposure to HIV, and metabolic dysregulation associated with antiretroviral therapy (ART). Measures of allostatic load, a physiologic indicator of weathering, can reflect biologic changes attributed to chronic stress across the lifespan, including that associated with living with HIV. Evaluation of allostatic load in the aging population of young adult PWH, especially in individuals with perinatally-acquired HIV (PHIV), has the potential to elucidate biologic mechanisms that predispose to adverse reproductive and sexual health and accelerated reproductive aging in this population. This proposal for Pediatric HIV/AIDS Cohort Study (PHACS) RISE Project 2: Reproductive and Sexual Health summarizes a 5-year research plan to evaluate the association of allostatic load with adverse pregnancy outcomes, reproductive aging, and subfertility in PWH, within the context of social drivers of health (SDoH). Leveraging the existing PHACS data, biospecimens, and infrastructure, along with a contemporary translational science approach, this observational investigation will measure metabolic, inflammation, stress, and reproductive biomarkers retrospectively in previously enrolled pregnant PWH and prospectively among newly recruited pregnant PWH, non-pregnant female PWH, and males with PHIV. This proposal will further evaluate the association of vaginal metabolome and microbiome signatures with persistence of cervical high-risk human papillomavirus (hrHPV) in PWH who are enrolled in the PHACS-affiliated LiVes LLC study of hrHPV in female PWH. In addition to biological assessments of allostatic load and surveys of participant reproductive and sexual health history and symptoms, we will assess three SDoH domains – the neighborhood context and environment, social and community support, and food security and nutrition – and perform medical record review at entry and again one year following enrollment. Aim 1 will evaluate the association of allostatic load with adverse pregnancy outcomes among pregnant PWH overall and by HIV disease duration, timing of ART initiation, PHIV status, and SDoH exposure profiles. Aim 2 will evaluate the association of allostatic load with reproductive aging and subfertility among male and female PWH overall and by PHIV status and SDoH exposure profiles. Aim 3 will evaluate the association of vaginal metabolome and microbiome biomarkers, which may be influenced by allostatic load, with hrHPV persistence, including by PHIV status and SDoH profiles, among PWH. PHACS RISE Project 2 will fill a crucial evidence gap on mechanisms by which allostatic load, SDoH, and HIV disease and treatment characteristics collectively modulate reproductive health and aging across the lifespan among PWH. Understanding these fundamental relationships may yield valuable insights to improve screening and develop individualized therapeutic interventions to promote optimal reproductive health among PWH.
