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Clin Infect Dis. 2018 Sep 14. doi: 10.1093/cid/ciy781. [Epub ahead of print]

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.

Author information

1
Department of Medicine, University of California - San Francisco School of Medicine; San Francisco, CA, United States.
2
Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health; Boston, MA, United States.
3
University of Texas Health Science Center at Houston, McGovern Medical School; Houston, TX, United States.
4
Cardiology Division, Brigham and Women's Hospital and Harvard Medical School; Boston, MA.
5
University of Cincinnati College of Medicine; Cincinnati, OH, United States.
6
David Geffen School of Medicine at University of California - Los Angeles; Los Angeles, CA, United States.
7
Cardiology Division, Massachusetts General Hospital and Harvard Medical School; Boston, MA, United States.
8
Case Western Reserve University School of Medicine; Cleveland, OH, United States.
9
University of Wisconsin School of Medicine and Public Health; Madison, WI, United States.

Abstract

Background:

Chronic inflammation in treated human immunodeficiency virus (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 II randomized, double-blind, multi-center trial in adults with treated HIV ≥40 years old with CD4+ T-cells ≥400 cells/mm 3 and with or at increased risk for ASCVD. Participants received LDMTX (5 to15 mg/week) or placebo (+ 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 versus 5 (5.6%) in the placebo group (=7.2%, upper 1-sided 90% CI=13.4%; pnon-inferiority=0.037). Week 24 change in FMD was 0.47% with LDMTX and 0.09% with placebo (p=0.55). No inflammatory markers changed differentially with LDMTX compared to placebo.

Conclusion:

In adults with HIV with or at increased risk for ASCVD, participants treated with LDMTX had more safety events than with placebo but the pre-specified non-inferiority 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.

PMID:
30219823
DOI:
10.1093/cid/ciy781

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