Safety and Impact of Low-dose Methotrexate on Endothelial Function and Inflammation in Individuals With Treated Human Immunodeficiency Virus: AIDS Clinical Trials Group Study A5314.

Autor: Hsue PY; Department of Medicine, University of California, San Francisco School of Medicine, Boston, Massachusetts., Ribaudo HJ; Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts., Deeks SG; Department of Medicine, University of California, San Francisco School of Medicine, Boston, Massachusetts., Bell T; McGovern Medical School, University of Texas Health Science Center at Houston, Boston, Massachusetts., Ridker PM; Cardiology Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Fichtenbaum C; University of Cincinnati College of Medicine, Ohio., Daar ES; David Geffen School of Medicine, University of California, Los Angeles, Boston., Havlir D; Department of Medicine, University of California, San Francisco School of Medicine, Boston, Massachusetts., Yeh E; Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts., Tawakol A; Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston., Lederman M; Case Western Reserve University School of Medicine, Cleveland, Ohio., Currier JS; David Geffen School of Medicine, University of California, Los Angeles, Boston., Stein JH; University of Wisconsin School of Medicine and Public Health, Madison.
Jazyk: angličtina
Zdroj: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2019 May 17; Vol. 68 (11), pp. 1877-1886.
DOI: 10.1093/cid/ciy781
Abstrakt: Background: Chronic inflammation in treated HIV infection is associated with mortality and atherosclerotic cardiovascular disease (ASCVD). We evaluated the safety and potential efficacy of low-dose methotrexate (LDMTX) in treated HIV.
Methods: This was a phase 2 randomized, double-blind, multicenter trial in adults ≥40 years old with treated HIV, with CD4+ T-cell count ≥400 cells/μL and with/at increased risk for ASCVD. Participants received LDMTX (5-15 mg/week) or placebo (plus folic acid) for 24 weeks and were followed for an additional 12 weeks. Primary endpoints were safety and brachial artery flow-mediated dilation (FMD).
Results: The 176 participants (90% male) had a median (Q1, Q3) age of 54 (49, 59) years. LDMTX was associated with decreases in CD4+ T cells at week 24 and CD8+ T cells at weeks 8, 12, and 24. Eleven participants (12.8%) experienced safety events in the LDMTX group vs 5 (5.6%) in placebo (Δ = 7.2%, upper 1-sided 90% CI, 13.4%; Pnoninferiority = .037). Week 24 change in FMD was 0.47% with LDMTX and 0.09% with placebo (P = .55). No inflammatory markers changed differentially with LDMTX compared to placebo.
Conclusions: Adults with HIV and increased ASCVD risk treated with LDMTX had more safety events than with placebo, but the prespecified noninferiority margin of 15% was not exceeded. LDMTX had no significant effect on endothelial function or inflammatory biomarkers but was associated with a significant decrease in CD8+ T cells. The balance of risks and potential benefits of LDMTX in this population will require additional investigation.
Clinical Trials Registration: NCT01949116.
(© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze: MEDLINE