The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy
| Autor: | 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 |
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| Přispěvatelé: | Internal Medicine, Medical Microbiology & Infectious Diseases, Biochemistry, Pharmacy, Virology, Immunology, Pathology, Urology |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Science Advances, 9 Science Advances, 9, 11 Science advances, 9(11):eade6675. American Association for the Advancement of Science |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.ade6675 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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