ArticleThe Journal of clinical investigation2022
Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Coadministration of rapamycin with a DNA/MVA SIV vaccine improves memory CD8+ T cell response.JCI insight · 2026Article
- Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.Nature communications · 2025Article
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Applications and limitations of the passenger hypothesis for HIV reservoir persistence and cure.Journal of virology · 2025Review
- Rapamycin enhances CAR-T control of HIV replication and reservoir elimination in vivo.The Journal of clinical investigation · 2025Article
- Article
- Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.Cell reports. Medicine · 2024Article
- Impact of alemtuzumab-mediated lymphocyte depletion on SIV reservoir establishment and persistence.PLoS pathogens · 2024Article
- Quantitative and Qualitative Distinctions between HIV-1 and SIV Reservoirs: Implications for HIV-1 Cure-Related Studies.Viruses · 2024Review
- 2-Hydroxypropyl-β-Cyclodextrin Treatment Induces Modest Immune Activation in Healthy Rhesus Macaques.Journal of virology · 2023Article
- Recent advances of the mammalian target of rapamycin signaling in mesenchymal stem cells.Frontiers in genetics · 2022Review
- HIV-1 replication and latency are balanced by mTOR-driven cell metabolism.Frontiers in cellular and infection microbiology · 2022Review
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 1 country.
Funding
Abstract
Proliferation of latently infected CD4+ T cells with replication-competent proviruses is an important mechanism contributing to HIV persistence during antiretroviral therapy (ART). One approach to targeting this latent cell expansion is to inhibit mTOR, a regulatory kinase involved with cell growth, metabolism, and proliferation. Here, we determined the effects of chronic mTOR inhibition with rapamycin with or without T cell activation in SIV-infected rhesus macaques (RMs) on ART. Rapamycin perturbed the expression of multiple genes and signaling pathways important for cellular proliferation and substantially decreased the frequency of proliferating CD4+ memory T cells (TM cells) in blood and tissues. However, levels of cell-associated SIV DNA and SIV RNA were not markedly different between rapamycin-treated RMs and controls during ART. T cell activation with an anti-CD3LALA antibody induced increases in SIV RNA in plasma of RMs on rapamycin, consistent with SIV production. However, upon ART cessation, both rapamycin and CD3LALA-treated and control-treated RMs rebounded in less than 12 days, with no difference in the time to viral rebound or post-ART viral load set points. These results indicate that, while rapamycin can decrease the proliferation of CD4+ TM cells, chronic mTOR inhibition alone or in combination with T cell activation was not sufficient to disrupt the stability of the SIV reservoir.
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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.