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.

TitleSafety and Impact of Low-Dose Methotrexate on Endothelial Function and Inflammation in Individuals with Treated Human Immunodeficiency Virus: AIDS Clinical Trials Group Study A5314.
Publication TypeJournal Article
Year of Publication2018
AuthorsHsue PY, Ribaudo HJ, Deeks SG, Bell T, Ridker PM, Fichtenbaum C, Daar ES, Havlir D, Yeh E, Tawakol A, Lederman M, Currier JS, Stein JH
JournalClin Infect Dis
Date Published2018 Sep 14
ISSN1537-6591
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.

DOI10.1093/cid/ciy781
Alternate JournalClin. Infect. Dis.
PubMed ID30219823
Grant ListUM1 AI069471 / AI / NIAID NIH HHS / United States