Pediatric HIV/aids cohort study (PHACS): research on immune aging, sexual and reproductive health, and perinatal acquisition: elucidating relationships in HIV (RISE) - cumulative stress burden over…

The National Institute of Allergy and Infectious Diseases awarded the President and Fellows of Harvard College (Harvard T.H. Chan School of Public Health) $24.97 million in cooperative agreement funding on September 12, 2025, for the Pediatric HIV/AIDS Cohort Study (PHACS): Research on Immune Aging, Sexual and Reproductive Health, and Perinatal Acquisition: Elucidating Relationships in HIV (RISE) program, a five-year initiative running through August 31, 2030.

The PHACS RISE program assembles and follows a prospective cohort of over 700 men and women with perinatally-acquired and non-perinatally-acquired HIV across seven U.S. clinical sites to investigate how cumulative stress and allostatic load—biological responses to chronic psychosocial and environmental stressors—drive immune aging, comorbidities, adverse reproductive outcomes, and reproductive aging in people with HIV. The program comprises two research projects: Project 1 examines immune aging, chronic stress pathways, and comorbidities in the context of antiretroviral therapy and viral reservoir burden; Project 2 evaluates associations between allostatic load, adverse pregnancy outcomes, reproductive aging, subfertility, and cervical high-risk human papillomavirus persistence in pregnant and non-pregnant women with HIV, with collection of metabolic, inflammation, stress, and reproductive biomarkers alongside vaginal metabolome and microbiome characterization. Two supporting cores—the Scientific and Administrative Core and the Data Management and Analysis Core—provide cross-cutting infrastructure to advance the research.

Work is performed at Boston, Massachusetts. Sub-recipients operate clinical sites and provide scientific leadership: Health Plus Hospitals Corp./Jacobi Medical Center (New York), The Research Foundation/SUNY Downstate Medical Center (New York), Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, University of Miami, Children's Research Institute (Washington, DC), and St. Jude Children's Research Hospital (Memphis, Tennessee) each serve as clinical enrollment sites targeting 10 participants annually. Northwestern University, Massachusetts General Hospital, and Ann and Robert H. Lurie Children's Hospital contribute to scientific and administrative leadership. Westat provides protocol development, compliance documentation, and study coordination support. Frontier Science & Technology Research Foundation manages the data management and analysis infrastructure, database systems, electronic case report forms, quality assurance, and specimen coordination. University of North Carolina at Chapel Hill provides protocol leadership and study design expertise.

Pediatric HIV/aids cohort study (PHACS): research on immune aging, sexual and reproductive health, and perinatal acquisition: elucidating relationships in HIV (RISE) - cumulative stress burden over the life course may elevate the risk of comorbidities, immune aging, reproductive aging, and adverse reproductive health outcomes that often affect people with HIV (PWH), and especially men and women with perinatally-acquired HIV (PHIV). The concept of allostatic load (AL) refers to biological responses to chronic stress, including exposure to adverse non-medical factors. AL may explain the development of accelerated aging and comorbidities among PWH, including those with PHIV, as well as the adverse health conditions experienced by populations with exposure to chronic stress. Few HIV research programs have jointly investigated drivers of aging and poor reproductive health in younger PWH, including those with PHIV, through an integrated approach, applying the lens of cumulative stress (AL) and non-medical factors. With the PHACS research on immune aging, supporting reproductive health, and perinatal acquisition: elucidating relationships in HIV (RISE) U19 program, we will close this GAP through two linked projects (project 1 - immune aging; project 2 - reproductive health). These cutting-edge projects will be supported by two cores (scientific and administrative core; data management and analysis core) to promote high-impact science that improves the health of PWH across the lifespan. Aim 1 of the PHACS RISE program is to assemble a prospective cohort of over 700 men and women with PHIV and women PWH (both PHIV and non-PHIV [nphiv]) across 7 US sites. Aim 2 is to elucidate pathways of chronic stress (as reflected by AL), immune aging, and comorbidities in the context of HIV, art, perinatal HIV acquisition, and HIV viral reservoir burden (project 1). Aim 3 is to elucidate pathways of chronic stress (AL), adverse pregnancy outcomes, reproductive aging, and human papilloma virus persistence in the context of HIV, art, and perinatal HIV acquisition (project 2). Through a consortium of seven experienced U.S.-based clinical sites and an expert multidisciplinary team of investigators, we will build on years of NIH investment and foundational cohorts in PHACS. We have RE-designed the PHACS network to establish a new, unified, and streamlined protocol, PHACS RISE. By leveraging well-curated existing data, comprehensively phenotyped cohorts of men and women with PHIV, rich specimen repositories, and the robust research infrastructure of PHACS, we will advance research in PWH, including those with PHIV, towards discovery of insights around the downstream repercussions of modifiable factors. PHACS RISE aims to bridge gaps in knowledge around our central theme - the interplay of HIV, chronic stress, aging, and reproductive health - and inform future studies around prevention and potential interventions against HIV aging-related comorbidites and adverse reproductive health.