Evidence map›Paper›PMID 30219823›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019

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.

Priscilla Y Hsue, Heather J Ribaudo, Steven G Deeks, Tanvir Bell, Paul M Ridker, Carl Fichtenbaum, Eric S Daar, Diane Havlir, Eunice Yeh, Ahmed Tawakol and 3 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01949116 (Effect of Reducing Inflammation With Low Dose Methotrexate on Inflammatory Markers and Endothelial Function in Treated and Suppressed HIV Infection), which is not on this map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01949116 phase2completednot on this map

Effect of Reducing Inflammation With Low Dose Methotrexate on Inflammatory Markers and Endothelial Function in Treated and Suppressed HIV Infection

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2014 to 2016Enrolled176ConditionsHIV InfectionsArmsLDMTX, Placebo, Folic acid
3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Adjunct Therapy for CD4Frontiers in immunology · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 9 institutions in 1 country.

Priscilla Y HsueDepartment of Medicine, University of California, San Francisco School of Medicine, Boston, Massachusetts.
Heather J RibaudoCenter for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Steven G DeeksDepartment of Medicine, University of California, San Francisco School of Medicine, Boston, Massachusetts.
Tanvir BellMcGovern Medical School, University of Texas Health Science Center at Houston, Boston, Massachusetts.
Paul M RidkerCardiology Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Carl FichtenbaumUniversity of Cincinnati College of Medicine, Ohio.
Eric S DaarDavid Geffen School of Medicine, University of California, Los Angeles, Boston.
Diane HavlirDepartment of Medicine, University of California, San Francisco School of Medicine, Boston, Massachusetts.
Eunice YehCenter for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Ahmed TawakolCardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston.
Michael LedermanCase Western Reserve University School of Medicine, Cleveland, Ohio.
Judith S CurrierDavid Geffen School of Medicine, University of California, Los Angeles, Boston.
James H SteinUniversity of Wisconsin School of Medicine and Public Health, Madison.
University of California, San Francisco · USCancer Research And Biostatistics · USUniversity of California, Los Angeles · USHarvard University · USMassachusetts General Hospital · USThe University of Texas Health Science Center at Houston · USUniversity of Cincinnati Medical Center · USUniversity of Wisconsin–Madison · USUniversity School · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1M
Statistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010
$71.9M
UCLA AIDS Prevention and Treatment Clinical Trials UnitUM1AI069424 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Judith S. Currier, RAPHAEL J LANDOVITZ · 2012 to 2026
$51.8M
WG3: HIV, Co-infections and Co-morbiditiesP30AI036219 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI Sharon L. Hillier, JONATHAN KARN · 1994 to 2026
$50.0M
Northwestern University Clinical Trial UnitUM1AI069471 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Chad J Achenbach · 2012 to 2026
$24.6M
Effect of low dose methotrexate on endothelial function and inflammation in HIVR01HL117713 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HSUE, PRISCILLA Y., STEIN, JAMES H · 2012 to 2016
$2.2M
NHLBI NIH HHS R01 HL117713NIAID NIH HHS P30 AI036219NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI068636NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069424NIAID NIH HHS UM1 AI069471
6 · The paper itself

Abstract

backgroundChronic 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.

methodsThis 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).

resultsThe 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.

conclusionsAdults 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.

Indexed as

Anti-Inflammatory AgentsAntiretroviral Therapy, Highly ActiveAtherosclerosisCD4 Lymphocyte CountDose-Response Relationship, DrugDouble-Blind MethodEndotheliumFemaleHIV-1HIV InfectionsHumansInflammationMaleMethotrexateMiddle AgedAnti-Inflammatory AgentsMethotrexateendothelial functionhuman immunodeficiency virusinflammation

Identifiers

PMID30219823
PMCPMC6522677
OpenAlexW2890416705

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.