ArticleProceedings of the National Academy of Sciences of the United States of America2018
Estrogen receptor-1 is a key regulator of HIV-1 latency that imparts gender-specific restrictions on the latent reservoir.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
131 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- Transcriptome profiles of latently- and reactivated HIV-1 infected primary CD4Frontiers in immunology · 2022Pooled it
- Sex Differences in Neurocognitive Function in Adults with HIV: Patterns, Predictors, and Mechanisms.Current psychiatry reports · 2019Pooled it
- Age modifies the association between sex and the plasma inflammatory proteome in treated HIV.The Journal of clinical investigation · 2026Trial
- Impact of Tamoxifen on Vorinostat-Induced Human Immunodeficiency Virus Expression in Women on Antiretroviral Therapy: AIDS Clinical Trials Group A5366, The MOXIE Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Participant Perspectives in an HIV Cure-Related Trial Conducted Exclusively in Women in the United States: Results from AIDS Clinical Trials Group 5366.AIDS research and human retroviruses · 2020Trial
- Time to viral rebound and safety after antiretroviral treatment interruption in postpartum women compared with men.AIDS (London, England) · 2019Trial
- Efficacy of postmenopausal estrogen replacement in SIV-infected female macaques on antiretroviral therapy.bioRxiv : the preprint server for biology · 2026Article
- Temporal trends in viral setpoint and peak CD4 + cell count soon after HIV-1 seroconversion.AIDS (London, England) · 2026Observational
- Effect of ligands and HIV latency-reversing agents on estrogen receptor α in CD4+ T cells.JCI insight · 2026Article
- HIV-1 viral load and reservoir size remain stable following SARS-CoV-2 mRNA vaccination in people with HIV.HIV medicine · 2026Article
- Impact of sex differences in adult and paediatric HIV-1 cure.Current opinion in HIV and AIDS · 2026Review
- The HIV Reservoir and Immune Landscape Across the Life Course of Women: Implications for Cure Strategies.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- CircRNA profiles of extracellular vesicle-enriched fractions from ART suppressed pregnant women living with HIV identifies interactome networks key to inflammation and viral latency.Journal of translational medicine · 2026Article
- Association between sex hormones and innate cytotoxic capacity of circulating and rectal mucosal immune cells.Clinical immunology communications · 2026Article
- Sex differences in immune responses to viruses, bacteria and vaccines.Nature immunology · 2026Review
- Network Pharmacology-Guided Identification ofInternational journal of molecular sciences · 2026Article
- Article
- Sex-Specific Factors Influencing HIV Infection.Immunological reviews · 2026Review
- Immune and hematologic alterations associated with CD4AIDS research and therapy · 2026Article
- Viral shedding and symptom severity across populations during acute COVID in the ACTIV-2 study.medRxiv : the preprint server for health sciences · 2026Article
71 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Unbiased shRNA library screens revealed that the estrogen receptor-1 (ESR-1) is a key factor regulating HIV-1 latency. In both Jurkat T cells and a Th17 primary cell model for HIV-1 latency, selective estrogen receptor modulators (SERMs, i.e., fulvestrant, raloxifene, and tamoxifen) are weak proviral activators and sensitize cells to latency-reversing agents (LRAs) including low doses of TNF-α (an NF-κB inducer), the histone deacetylase inhibitor vorinostat (soruberoylanilide hydroxamic acid, SAHA), and IL-15. To probe the physiologic relevance of these observations, leukapheresis samples from a cohort of 12 well-matched reproductive-age women and men on fully suppressive antiretroviral therapy were evaluated by an assay measuring the production of spliced envelope (env) mRNA (the EDITS assay) by next-generation sequencing. The cells were activated by T cell receptor (TCR) stimulation, IL-15, or SAHA in the presence of either β-estradiol or an SERM. β-Estradiol potently inhibited TCR activation of HIV-1 transcription, while SERMs enhanced the activity of most LRAs. Although both sexes responded to SERMs and β-estradiol, females showed much higher levels of inhibition in response to the hormone and higher reactivity in response to ESR-1 modulators than males. Importantly, the total inducible RNA reservoir, as measured by the EDITS assay, was significantly smaller in the women than in the men. We conclude that concurrent exposure to estrogen is likely to limit the efficacy of viral emergence from latency and that ESR-1 is a pharmacologically attractive target that can be exploited in the design of therapeutic strategies for latency reversal.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.