Evidence map›Paper›PMID 37581929›Full record

ArticleJCI insight2023

The latency-reversing agent HODHBt synergizes with IL-15 to enhance cytotoxic function of HIV-specific T cells.

Dennis C Copertino, Carissa S Holmberg, Jared Weiler, Adam R Ward, J Natalie Howard, Callie Levinger, Alina Ps Pang, Michael J Corley, Friederike Dündar, Paul Zumbo and 14 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. Cytotoxic CD4Signal transduction and targeted therapy · 2026
    Review
  2. Searching for a HIV-1 Cure.Theranostics · 2026
    Review
  3. Review
  4. Article
  5. Article
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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

24 authors at 7 institutions in 5 countries.

Dennis C CopertinoInfectious Diseases Division, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Carissa S HolmbergDepartment of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.
Jared WeilerInfectious Diseases Division, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Adam R WardInfectious Diseases Division, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
J Natalie HowardDepartment of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.
Callie LevingerDepartment of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.
Alina Ps PangInfectious Diseases Division, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Michael J CorleyInfectious Diseases Division, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Friederike DündarApplied Bioinformatics Core and.
Paul ZumboApplied Bioinformatics Core and.
Doron BetelInfectious Diseases Division, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Rajesh T GandhiDivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
Deborah K McMahonDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Ronald J BoschCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Noemi LindenInfectious Diseases Division, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Bernard J MacatangayDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Joshua C CyktorDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Joseph J EronDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
John W MellorsDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Colin KovacsMaple Leaf Medical Clinic, Toronto, Ontario, Canada.
Erika BenkoMaple Leaf Medical Clinic, Toronto, Ontario, Canada.
Alberto BosqueDepartment of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.
R Brad JonesInfectious Diseases Division, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
AIDS Clinical Trials Group (ACTG) A5321 Team
Cornell University · USGeorge Washington University · USUniversity of Pittsburgh · USMaple Leaf Medical Clinic · CABoston University · USMassachusetts General Hospital · USUniversity of North Carolina at Chapel Hill · 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
The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4M
Harvard Medical School Vaccine Clinical Trials UnitUM1AI069412 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Lindsey Robert Baden, Daniel R. Kuritzkes · 2012 to 2026
$57.2M
Weill Cornell Medicine - Rutgers New Jersey Medical School Clinical Trials UnitUM1AI069419 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI ROY M. GULICK · 2012 to 2026
$44.6M
University of Pittsburgh Clinical Trials UnitUM1AI069494 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SUSAN L KOLETAR, John W Mellors · 2012 to 2026
$38.0M
REACH: Research Enterprise to Advance a Cure for HIVUM1AI164565 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI Marina Caskey, R. Brad Jones · 2021 to 2026
$32.9M
SWG 2: Cure Research Scientific Working GroupP30AI117970 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI Italo Mocchetti · 2015 to 2026
$29.6M
Seattle Vaccine Trials UnitUM1AI069481 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Rachel Ann Bender Ignacio, Margaret Juliana McElrath · 2012 to 2026
$24.4M
A family of compounds that reactivate latent HIV without T cell activationR33AI116212 · NIAID · UNIVERSITY OF UTAH · PI BOSQUE, ALBERTO · 2016 to 2018
$1.4M
Training in HIV Persistence, Co-morbidities and TherapeuticsT32AI158105 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI BOSQUE, ALBERTO, MAGGIRWAR, SANJAY B. · 2021 to 2025
$909k
NIAID NIH HHS P30 AI060354NIAID NIH HHS P30 AI117970NIAID NIH HHS R33 AI116212NIAID NIH HHS R56 AI145683NIAID NIH HHS T32 AI158105NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069412NIAID NIH HHS UM1 AI069419NIAID NIH HHS UM1 AI069481NIAID NIH HHS UM1 AI069494NIAID NIH HHS UM1 AI106701NIAID NIH HHS UM1 AI164565
6 · The paper itself

Abstract

IL-15 is under clinical investigation toward the goal of curing HIV infection because of its abilities to reverse HIV latency and enhance immune effector function. However, increased potency through combination with other agents may be needed. 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one (HODHBt) enhances IL-15-mediated latency reversal and NK cell function by increasing STAT5 activation. We hypothesized that HODHBt would also synergize with IL-15, via STAT5, to directly enhance HIV-specific cytotoxic T cell responses. We showed that ex vivo IL-15 + HODHBt treatment markedly enhanced HIV-specific granzyme B-releasing T cell responses in PBMCs from antiretroviral therapy-suppressed (ART-suppressed) donors. We also observed upregulation of antigen processing and presentation in CD4+ T cells and increased surface MHC-I. In ex vivo PBMCs, IL-15 + HODHBt was sufficient to reduce intact proviruses in 1 of 3 ART-suppressed donors. Our findings reveal the potential for second-generation IL-15 studies incorporating HODHBt-like therapeutics. Iterative studies layering on additional latency reversal or other agents are needed to achieve consistent ex vivo reservoir reductions.

Indexed as

Antineoplastic AgentsHIV InfectionsHumansInterleukin-15STAT5 Transcription FactorT-Lymphocytes, CytotoxicTriazinesVirus LatencyAntineoplastic AgentsHODHBtInterleukin-15STAT5 Transcription FactorTriazinesAdaptive immunityAIDS/HIVCellular immune responseImmunologyImmunotherapy

Identifiers

PMID37581929
PMCPMC10561764
OpenAlexW4385840317

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.