Brief Report: Low-Dose Methotrexate Does Not Affect Measures of HIV-1 Persistence in Individuals With Chronically Treated HIV-1 Infection.

Autor:	Cyktor JC; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Yeh E; Department of Biostatistics, Harvard TH Chan Sch Public Health, Boston, MA., Ribaudo H; Department of Biostatistics, Harvard TH Chan Sch Public Health, Boston, MA., Hoeth D; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Naqvi A; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Bell T; The University of Texas Health Science Center at Houston, Houston, TX., Ridker PM; Center for Cardiovascular Disease Prevention, Cardiology Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Fichtenbaum C; Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH., Daar ES; Lundquist Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine, University of California, Los Angeles, CA., Havlir D; University of California, Biostatistics, Epidemiology, and Computational Precision Health, Berkeley, CA., Tawakol A; Cardiovascular Imaging Research Center and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA., Lederman MM; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH., Stein JH; Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI., Deeks SG; Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco, CA., Currier JS; Division of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA; and., Hsue PY; Division of Cardiology, Department of Medicine, University of California, San Francisco, CA., Mellors JW; Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Jazyk:	angličtina
Zdroj:	Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2024 Aug 15; Vol. 96 (5), pp. 481-485.
DOI:	10.1097/QAI.0000000000003453
Abstrakt:	Background: People with HIV-1 often have chronic inflammation leading to severe non-AIDS morbidity and mortality. The AIDS Clinical Trials Group Study A5314 sought to lower inflammation with low-dose methotrexate (LDMTX). The primary study outcomes were reported previously but here we present the impact of LDMTX on multiple measures of HIV-1 persistence. Methods: A5314 was a phase 2 randomized, double-blind, multicenter trial in 176 adult people with HIV-1 on virally suppressive antiretroviral therapy. LDMTX (5-15 mg/wk) was administered for 24 weeks with an additional 12 weeks of participant follow-up. The current analyses of HIV-1 persistence were restricted to 60 participants (30 LDMTX and 30 placebo) randomly selected from the total population. Plasma HIV-1 RNA, total HIV-1 DNA, and cell-associated HIV-1 RNA (CA HIV-1 RNA) were measured by sensitive quantitative PCR assays. Results: LDMTX treatment had no significant effect on sensitive measures of plasma HIV-1 RNA, HIV-1 DNA, CA HIV-1 RNA, or CA HIV-1 RNA/DNA ratio at any time point or from baseline to week 24. As observed in the main study, absolute peripheral CD4+ and CD8+ T-cell numbers decreased from baseline to week 24 among the 30 participants receiving LDMTX compared with placebo (median decrease of -31.5 CD4+ T cells/µL, -83.5 CD8+ T cells/µL). Conclusions: LDMTX had no significant effect on any measure of HIV-1 persistence in plasma or peripheral blood mononuclear cells. Further studies are needed to determine whether other immunosuppressive and/or immunoreductive interventions are safe and capable of affecting HIV-1 persistence. Competing Interests: Supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636, and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. J.W.M. is a paid consultant to Gilead Sciences, receives research funding from Gilead Sciences through the University of Pittsburgh, receives compensation from Abound Bio, Inc., and owns shares options in MingMed, Galapagos, and Infectious Disease Connect, all unrelated to the current work. The remaining authors have no funding or conflicts of interest to disclose. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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