The HIV Reservoir and Immune Landscape Across the Life Course of Women: Implications for Cure Strategies
Year: 2026
Type: article
Abstract: Sex hormones and reproductive transitions profoundly shape immune, metabolic, neuropsychological, and mucosal biology, as well as HIV persistence, across women's lives. Although women constitute the majority of people with HIV worldwide, hormonal and reproductive biology are still not sufficiently incorporated into HIV cure research. Cisgender women, transgender women on gender-affirming hormone therapy (GAHT), and gender-diverse individuals assigned female at birth are underrepresented in cure studies, despite experiencing unique and changing hormonal states that influence estrogen signaling, tissue-specific hormone exposure, and immune function. Estradiol, progesterone, and hormone-based therapies, including contraception, GAHT, and menopausal hormone therapy, influence innate and adaptive immunity, inflammatory responses, epithelial barrier function, and cardiometabolic and neurocognitive pathways. These processes also shape tissue-specific HIV reservoir formation and maintenance, modulate proviral transcription, and affect immune effector functions. However, most HIV cure strategies have been developed without systematically considering these hormone-dependent mechanisms, which limits mechanistic understanding, broad applicability, and translational relevance. In this review, we synthesize emerging evidence at the intersection of reproductive endocrinology and HIV immunovirology, identify critical knowledge gaps, and propose priorities for life-course, hormone-informed HIV cure strategies. We argue that meaningful inclusion of women and gender-diverse individuals is essential not only for ethically grounded, equity-centered, community-engaged research practices but also for the scientific rigor needed to achieve durable ART-free virologic control and cure.
DOI: 10.1111/aji.70279
Authors: Elizabeth Hastie, Priya Khetan, Sarah A. LaMere, Ashley F. George, Rebecca Abelman, Kathleen Weber, Phyllis C. Tien, Judith D. Auerbach, Maile Karris, Todd Brown, Jonathan Karn, Loreen Willenberg, Dawn Averitt, Bridgette Picou, Nadia R. Roan, Eileen P. Scully, Karine Dubé, Nancie Archin, Sara Gianella
Institutions: University of California San Diego, University of North Carolina at Chapel Hill, Gladstone Institutes, University of California, San Francisco, University of California San Francisco Medical Center, Hektoen Institute, San Francisco VA Health Care System, Johns Hopkins University, Johns Hopkins Medicine, Case Western Reserve University, The Wistar Institute
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,460
Funders: amfAR, The Foundation for AIDS Research, Merck, California HIV/AIDS Research Program, Gilead Sciences, Philadelphia Foundation, National Institutes of Health, U.S. Food and Drug Administration, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke
Awards: G2056520599, The Synergistic Effects of Menopause and HIV on Cardiovascular Disease Risk in Women, San Diego Center for AIDS Research (SD CFAR), Sex-differences in HIV persistence and Immune Dynamics during Reproductive Aging, BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy, Impact of Gender Affirming Hormone Therapy on HIV Viral Dynamics and Immune Responses in Transgender Women, HIV Reservoir Dynamics and Immune Responses Across the Female Reproductive Life Span, HOPE Training Grant
OpenAlex ID: W7168573558