The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy
| العنوان: | The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy |
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| المؤلفون: | Henrieke A. B. Prins, Raquel Crespo, Cynthia Lungu, Shringar Rao, Letao Li, Ronald J. Overmars, Grigorius Papageorgiou, Yvonne M. Mueller, Mateusz Stoszko, Tanvir Hossain, Tsung Wai Kan, Bart J. A. Rijnders, Hannelore I. Bax, Eric C. M. van Gorp, Jan L. Nouwen, Theodora E. M. S. de Vries-Sluijs, Carolina A. M. Schurink, Mariana de Mendonça Melo, Els van Nood, Angela Colbers, David Burger, Robert-Jan Palstra, Jeroen J. A. van Kampen, David A. M. C. van de Vijver, Thibault Mesplède, Peter D. Katsikis, Rob A. Gruters, Birgit C. P. Koch, Annelies Verbon, Tokameh Mahmoudi, Casper Rokx |
| المساهمون: | Internal Medicine, Medical Microbiology & Infectious Diseases, Biochemistry, Pharmacy, Virology, Immunology, Pathology, Urology |
| المصدر: | Science Advances, 9 Science Advances, 9, 11 Science advances, 9(11):eade6675. American Association for the Advancement of Science |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | All institutes and research themes of the Radboud University Medical Center, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Multidisciplinary, SDG 3 - Good Health and Well-being |
| الوصف: | Contains fulltext : 291084.pdf (Publisher’s version ) (Open Access) Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLWH, substantiating its potential advancement in clinical studies. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2375-2548 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c3887f3da1a82107e3f551dccee2edbTest https://doi.org/10.1126/sciadv.ade6675Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4c3887f3da1a82107e3f551dccee2edb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
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