Efficacy of postmenopausal estrogen replacement in SIV-infected female macaques on antiretroviral therapy.
- 1Oregon Health & Science University
Abstract
The success of modern antiretroviral therapy (ART) has increased the life expectancy of people living with HIV to levels approaching that of people without HIV. For women living with HIV (WLWH), this means that more will survive to undergo menopause and experience the consequences of decreased ovarian hormone levels, particularly estrogen (E2). The recent change in federal guidance for use of postmenopausal hormone therapy is increasing demand for both E2-alone and E2+progestogen formulations to control adverse symptoms of menopause. The consequences and efficacy of hormone therapy in WLWH are thus an important issue for WLWH and their healthcare providers. The role of E2 replacement in postmenopausal WLWH is a significant issue because of its potential effects on control of the viral reservoir and its demonstrated beneficial metabolic effects in postmenopausal women in the general population. To address these questions, we employed a novel nonhuman primate model of postmenopausal WLWH undergoing E2 replacement. Reproductively competent female rhesus macaques were infected with simian immunodeficiency virus (SIV) and then subjected to a daily ART regimen. After complete suppression of plasma viremia, all animals underwent ovariectomy (OVX) and were then implanted with Silastic capsules containing either cholesterol vehicle or sufficient E2 to restore pre-OVX plasma levels. Plasma and cell-associated viral dynamics, immune responses, body composition, systemic and tissue-specific metabolic parameters, cytokine profiles, and parameters of bone health were followed longitudinally from baseline through 34 weeks of E2 deficiency or replacement. We found that E2 status did not significantly affect plasma or tissue viral dynamics or overall metabolic homeostasis. However, E2 replacement exerted beneficial effects on several aspects of bone health despite the chronic inflammatory state that persisted following effective ART suppression of the SIV reservoir. Our findings suggest that hormone therapy, specifically E2 replacement, offers benefit to WLWH, particularly with respect to bone loss.
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BibTeX
@misc{webb2026efficacy,
title = {{Efficacy of postmenopausal estrogen replacement in SIV-infected female macaques on antiretroviral therapy.}},
author = {G. M. Webb and D. L. Takahashi and M. A. Kirigiti and S. R. Lindsley and H. Blomenkamp and C. Zaro and M. Shallman and C. M. McGuire and H. Hofmeister and C. Pessoa and A. McCullen and M. Humkey and V. Monfared and U. T. Iwaniec and R. T. Turner and L. Gao and O. Varlamov and P. C. Tien and J. T. Jensen and J. B. Sacha and P. Kievit and C. T. Roberts and K. A. Sauter},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.746440},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.746440v1},
note = {Public domain},
}
RIS
TY - UNPB
TI - Efficacy of postmenopausal estrogen replacement in SIV-infected female macaques on antiretroviral therapy.
AU - G. M. Webb
AU - D. L. Takahashi
AU - M. A. Kirigiti
AU - S. R. Lindsley
AU - H. Blomenkamp
AU - C. Zaro
AU - M. Shallman
AU - C. M. McGuire
AU - H. Hofmeister
AU - C. Pessoa
AU - A. McCullen
AU - M. Humkey
AU - V. Monfared
AU - U. T. Iwaniec
AU - R. T. Turner
AU - L. Gao
AU - O. Varlamov
AU - P. C. Tien
AU - J. T. Jensen
AU - J. B. Sacha
AU - P. Kievit
AU - C. T. Roberts
AU - K. A. Sauter
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.746440
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.746440v1
AB - The success of modern antiretroviral therapy (ART) has increased the life expectancy of people living with HIV to levels approaching that of people without HIV. For women living with HIV (WLWH), this means that more will survive to undergo menopause and experience the consequences of decreased ovarian hormone levels, particularly estrogen (E2). The recent change in federal guidance for use of postmenopausal hormone therapy is increasing demand for both E2-alone and E2+progestogen formulations to control adverse symptoms of menopause. The consequences and efficacy of hormone therapy in WLWH are thus an important issue for WLWH and their healthcare providers. The role of E2 replacement in postmenopausal WLWH is a significant issue because of its potential effects on control of the viral reservoir and its demonstrated beneficial metabolic effects in postmenopausal women in the general population. To address these questions, we employed a novel nonhuman primate model of postmenopausal WLWH undergoing E2 replacement. Reproductively competent female rhesus macaques were infected with simian immunodeficiency virus (SIV) and then subjected to a daily ART regimen. After complete suppression of plasma viremia, all animals underwent ovariectomy (OVX) and were then implanted with Silastic capsules containing either cholesterol vehicle or sufficient E2 to restore pre-OVX plasma levels. Plasma and cell-associated viral dynamics, immune responses, body composition, systemic and tissue-specific metabolic parameters, cytokine profiles, and parameters of bone health were followed longitudinally from baseline through 34 weeks of E2 deficiency or replacement. We found that E2 status did not significantly affect plasma or tissue viral dynamics or overall metabolic homeostasis. However, E2 replacement exerted beneficial effects on several aspects of bone health despite the chronic inflammatory state that persisted following effective ART suppression of the SIV reservoir. Our findings suggest that hormone therapy, specifically E2 replacement, offers benefit to WLWH, particularly with respect to bone loss.
ER -