ArticleProceedings of the National Academy of Sciences of the United States of America2008
Reduction of CCR5 with low-dose rapamycin enhances the antiviral activity of vicriviroc against both sensitive and drug-resistant HIV-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The trial behind it
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
47 citing papers in PubMed, 63 citations in OpenAlex.
- HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug.Journal of virology · 2012Trial
- Coadministration of rapamycin with a DNA/MVA SIV vaccine improves memory CD8+ T cell response.JCI insight · 2026Article
- Chemokine receptor type-5: a key regulator of immunity, disease pathogenesis, and emerging therapeutic target.Inflammopharmacology · 2025Review
- Efficacy of transcutaneous electrical acupoint stimulation for immunological non-responder in HIV/AIDS combined with amphetamine abuse: study protocol for a randomized controlled trial.BMC complementary medicine and therapies · 2024Article
- Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.Cell reports. Medicine · 2024Article
- mTOR regulation of metabolism limits LPS-induced monocyte inflammatory and procoagulant responses.Communications biology · 2022Article
- Identifying CCR5 coreceptor populations permissive for HIV-1 entry and productive infection: implications for in vivo studies.Journal of translational medicine · 2022Article
- Cure and Long-Term Remission Strategies.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Past HIV-1 Medications and the Current Status of Combined Antiretroviral Therapy Options for HIV-1 Patients.Pharmaceutics · 2021Review
- Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- The neuropsychiatric manifestations of COVID-19: Interactions with psychiatric illness and pharmacological treatment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy.Frontiers in immunology · 2021Review
- Review
- Organ transplantation in persons with HIV.AIDS (London, England) · 2020Review
- Article
- Modulation of mTORC1 Signaling Pathway by HIV-1.Cells · 2020Review
- Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy.Viruses · 2020Review
- New targets for HIV drug discovery.Drug discovery today · 2019Review
- CCR5 Inhibitors and HIV-1 Infection.Journal of AIDS and HIV treatment · 2019Article
- Kidney Disease in HIV: Moving beyond HIV-Associated Nephropathy.Journal of the American Society of Nephrology : JASN · 2017Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Vicriviroc (VCV) is a chemokine (C-C motif) receptor 5 (CCR5) antagonist with potent anti-HIV activity that currently is being evaluated in phase III clinical trials. In the present study, donor CCR5 density (CCR5 receptors/CD4 lymphocytes) inversely correlated with VCV antiviral activity (Spearman's correlation test; r = 0.746, P = 0.0034). Low doses of the transplant drug rapamycin (RAPA) reduced CCR5 density and enhanced VCV antiviral activity. In drug interaction studies, the RAPA/VCV combination had considerable antiviral synergy (combination indexes of 0.1-0.04) in both multicycle and single-cycle infection of lymphocytes. The synergy between RAPA and VCV translated into dose reduction indexes of 8- to 41-fold reductions for RAPA and 19- to 658-fold reductions for VCV. RAPA enhanced VCV antiviral activity against both B and non-B clade isolates, potently suppressing clade G viruses with reported reduced sensitivities to VCV and to the licensed CCR5 antagonist maraviroc. Importantly, RAPA reduction of CCR5 density in lymphocytes sensitized VCV-resistant strains to VCV, inhibiting virus production by approximately 90%. We further demonstrated the role of CCR5 density on VCV activity against resistant virus in donor lymphocytes and in cell lines expressing varying CCR5 densities. Together, these results suggest that low doses of RAPA may increase the durability of VCV-containing regimens in patients by enhancing VCV viral suppression, by allowing the use of lower doses of VCV with reduced potential for toxicity, and by controlling emerging VCV-resistant variants.
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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.