Evidence map›Paper›PMID 34169526›Full record

Trial reportJournal of clinical pharmacology2021

Pharmacokinetics of Ruxolitinib in HIV Suppressed Individuals on Antiretroviral Agent Therapy from the ACTG A5336 Study.

Selwyn J Hurwitz, Sijia Tao, Christina Gavegnano, Yong Jiang, Randall L Tressler, Athe Tsibris, Carlos Del Rio, Edgar T Overton, Michael M Lederman, Amy Kantor and 6 more

Open access · greenAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.1field-weighted citation impact, top 52% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.

  1. Pooled it
  2. The STAT Signaling Pathway in HIV-1 Infection: Roles and Dysregulation.International journal of molecular sciences · 2025
    Review
  3. Observational
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

16 authors at 8 institutions in 1 country.

Selwyn J HurwitzLaboratory of Biochemical Pharmacology, Emory Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Sijia TaoLaboratory of Biochemical Pharmacology, Emory Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Christina GavegnanoDepartment of Pathology and Laboratory Medicine and Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, Georgia, USA.
Yong JiangLaboratory of Biochemical Pharmacology, Emory Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Randall L TresslerNational Institutes of Health/National Institute of Allergy and Infectious Disease, Rockville, Maryland, USA.
Athe TsibrisBrigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Carlos Del RioDepartment of Medicine and Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Edgar T OvertonDivision of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Michael M LedermanCase Western Reserve University School of Medicine and University Hospitals/Case Medical Center, Cleveland, Ohio, USA.
Amy KantorHarvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Carlee MoserHarvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
James J KohlerLaboratory of Biochemical Pharmacology, Emory Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Jeffrey LennoxDivision of Infectious Diseases, Emory University School of Medicine and Grady Memorial Hospital, Atlanta, Georgia, USA.
Vincent C MarconiDivision of Infectious Diseases, Emory University School of Medicine and Rollins School of Public Health and Atlanta Veterans Affairs Medical Center, Decatur, Georgia, USA.
Charles W FlexnerDivisions of Clinical Pharmacology and Infectious Diseases, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Raymond F SchinaziLaboratory of Biochemical Pharmacology, Emory Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Emory University · USChildren's Healthcare of Atlanta · USHarvard University · USBrigham and Women's Hospital · USCase Western Reserve University · USJohns Hopkins University · USNational Institute of Allergy and Infectious Diseases · USUniversity of Alabama at Birmingham · 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
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026
$74.0M
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
Towards Suppression and Elimination of HIV in the CNSR01MH116695 · NIMH · EMORY UNIVERSITY · PI SCHINAZI, RAYMOND FELIX, TYOR, WILLIAM R · 2018 to 2022
$3.4M
Phase II study to evaluate the efficacy and safety of baricitinib for reduction of HIV in the central nervous systemR01MH128158 · NIMH · EMORY UNIVERSITY · PI Christina Gavegnano, Vincent Charles Marconi · 2022 to 2026
$3.2M
NIAID NIH HHS P30 AI050409NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701NIMH NIH HHS R01 MH116695NIMH NIH HHS R01 MH128158
6 · The paper itself

Abstract

Ruxolitinib is a US Food and Drug Administration-approved orally administered Janus kinase (1/2) inhibitor that reduces cytokine-induced inflammation. As part of a randomized, phase 2, open-label trial, ruxolitinib (10 mg twice daily) was administered to HIV-positive, virologically suppressed individuals (33 men, 7 women) on antiretroviral therapy (ART) for 5 weeks. Herein, we report the population PK subsequently determined from this study. Plasma concentrations of ruxolitinib (294 samples) and antiretroviral agents were measured at week 1 (N = 39 participants) and week 4 or 5 (N = 37). Ruxolitinib PK was adequately described with a 2-compartment model with first-order absorption and elimination with distribution volumes normalized to mean body weight (91.5 kg) and a separate typical clearance for participants administered efavirenz (a known cytochrome P450 3A4 inducer). Participants administered an ART regimen with efavirenz had an elevated typical apparent oral clearance versus the integrase inhibitor regimen group (22.5 vs 12.9 L/hr; N = 14 vs 25). Post hoc predicted apparent oral clearance was likewise more variable and higher (P < .0001) in those administered efavirenz. There was  an ≈25% variation in ruxolitinib plasma exposures between week 1 and week 4/5. ART plasma concentrations resembled those from PK studies without ruxolitinib. Therefore, integrase inhibitor-based ART regimens may be preferred over efavirenz-based regimens when ruxolitinib is administered to HIV-positive individuals.

Indexed as

AdultAlkynesAnti-Retroviral AgentsBenzoxazinesBody WeightCyclopropanesCytochrome P-450 CYP3A InducersDrug InteractionsFemaleHIV InfectionsHumansJanus KinasesMaleMetabolic Clearance RateMiddle AgedNitrilesAlkynesAnti-Retroviral AgentsBenzoxazinesCyclopropanesCytochrome P-450 CYP3A InducersefavirenzJanus KinasesNitrilesPyrazolesPyrimidinesruxolitinibantiretroviral agentsdrug-drug interactionsHIVNONMEM analysispopulation PKruxolitinib

Identifiers

PMID34169526
PMCPMC8599628
OpenAlexW3176089802

What OpenQuestion holds

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Registered trials

None linked

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.