Evidence map›Paper›PMID 33677480›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021

Impact of Anti-PD-1 and Anti-CTLA-4 on the Human Immunodeficiency Virus (HIV) Reservoir in People Living With HIV With Cancer on Antiretroviral Therapy: The AIDS Malignancy Consortium 095 Study.

Thomas A Rasmussen, Lakshmi Rajdev, Ajantha Rhodes, Ashanti Dantanarayana, Surekha Tennakoon, Socheata Chea, Tim Spelman, Shelly Lensing, Rachel Rutishauser, Sonia Bakkour and 9 more

Registry-linked trialOpen access · greenAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02408861 (A Phase I Study of Ipilimumab and Nivolumab in Advanced HIV Associated Solid Tumors With Expansion Cohort in HIV Associated Solid Tumors and a Cohort of HIV-Associated Classical Hodgkin Lymphoma), which is not on this map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 3% 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.

NCT02408861 phase1terminatednot on this map

A Phase I Study of Ipilimumab and Nivolumab in Advanced HIV Associated Solid Tumors With Expansion Cohort in HIV Associated Solid Tumors and a Cohort of HIV-Associated Classical Hodgkin Lymphoma

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2015 to 2024Enrolled79ConditionsAdvanced Malignant Solid Neoplasm, Anal Carcinoma, HIV Infection, Kaposi SarcomaArmsBiospecimen Collection, Bone Marrow Biopsy, Computed Tomography, Ipilimumab, Nivolumab
3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
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  15. Pathogens (Basel, Switzerland) · 2025
    Article
  16. Article
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  18. Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025
    Review
  19. Latency Reversing Agents and the Road to an HIV CurePathogens (Basel, Switzerland) · 2025
    Review
  20. Article
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

19 authors at 8 institutions in 2 countries.

Thomas A RasmussenThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.ORCID 0000-0001-5354-2442
Lakshmi RajdevDepartment of Haematology and Oncology, Lennox Hill Hospital, New York, New York, USA.
Ajantha RhodesThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.
Ashanti DantanarayanaThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.
Surekha TennakoonThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.
Socheata CheaThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.
Tim SpelmanThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.
Shelly LensingDepartment of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Rachel RutishauserDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Sonia BakkourVitalant Research Institute and Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.
Michael BuschVitalant Research Institute and Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.
Janet D SilicianoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Robert F SilicianoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mark H EinsteinDepartment of Obstetrics, Gynecology, and Reproductive Health, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
Dirk P DittmerLineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Elizabeth ChiaoBaylor College of Medicine, Houston, Texas, USA.
Steven G DeeksDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Christine DurandDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sharon R LewinThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.
The Royal Melbourne Hospital · AUUniversity of California, San Francisco · USJohns Hopkins University · USBaylor College of Medicine · USLenox Hill Hospital · USRutgers, The State University of New Jersey · USUniversity of Arkansas for Medical Sciences · USUniversity of North Carolina at Chapel Hill · US

Funding

Consortium for Advancing Management and Prevention of Cancer in People with HIVUM1CA121947 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Joseph A. Sparano · 2015 to 2026
$253.7M
University of Southern CaliforniaU01CA121947 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MITSUYASU, RONALD T. · 2006 to 2014
$54.7M
ART Modulation of Viral Pathogenesis in Oral EpitheliaR01DE018304 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DITTMER, DIRK P · 2007 to 2025
$6.9M
Mechanisms of KSHV TransmissionR01CA239583 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAMANIA, BLOSSOM A, DITTMER, DIRK P · 2019 to 2023
$2.8M
Impact of HIV on the Tumor MicroenvironmentR01CA228172 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAMANIA, BLOSSOM A, DITTMER, DIRK P · 2018 to 2022
$2.0M
American Foundation for AIDS Research 109226-58-RGRLAustralian Centre for HIV and Hepatitis ResearchAustralian National Health and Medical Research Council GNT1149990NCI NIH HHS R01 CA239583NCI NIH HHS UM1 CA121947NIDCR NIH HHS R01 DE018304
6 · The paper itself

Abstract

backgroundAntibodies to programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) may perturb human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) by reversing HIV latency and/or boosting HIV-specific immunity, leading to clearance of infected cells. We tested this hypothesis in a clinical trial of anti-PD-1 alone or in combination with anti-CTLA-4 in people living with HIV (PLWH) and cancer.

methodsThis was a substudy of the AIDS Malignancy Consortium 095 Study. ART-suppressed PLWH with advanced malignancies were assigned to nivolumab (anti-PD-1) with or without ipilimumab (anti-CTLA-4). In samples obtained preinfusion and 1 and 7 days after the first and fourth doses of immune checkpoint blockade (ICB), we quantified cell-associated unspliced (CA-US) HIV RNA and HIV DNA. Plasma HIV RNA was quantified during the first treatment cycle. Quantitative viral outgrowth assay (QVOA) to estimate the frequency of replication-competent HIV was performed before and after ICB for participants with samples available.

resultsOf 40 participants, 33 received nivolumab and 7 nivolumab plus ipilimumab. Whereas CA-US HIV RNA did not change with nivolumab monotherapy, we detected a median 1.44-fold increase (interquartile range, 1.16-1.89) after the first dose of nivolumab and ipilimumab combination therapy (P = .031). There was no decrease in the frequency of cells containing replication-competent HIV, but in the 2 individuals on combination ICB for whom we had longitudinal QVOA, we detected decreases of 97% and 64% compared to baseline.

conclusionsAnti-PD-1 alone showed no effect on HIV latency or the latent HIV reservoir, but the combination of anti-PD-1 and anti-CTL-4 induced a modest increase in CA-US HIV RNA and may potentially eliminate cells containing replication-competent HIV. CLINICAL TRIALS REGISTRATION: NCT02408861.

Indexed as

Acquired Immunodeficiency SyndromeHIV-1HIV InfectionsNeoplasmsCTLA-4 AntigenHumansProgrammed Cell Death 1 ReceptorVirus LatencyCTLA-4 AntigenProgrammed Cell Death 1 Receptoranti–CTLA-4anti–PD-1HIVHIV latency

Identifiers

PMID33677480
PMCPMC8492152
OpenAlexW3135286008

What OpenQuestion holds

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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.