ArticleAIDS (London, England)2018
Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency.
Article in AIDS (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Expression Profile and Biological Role of Immune Checkpoints in Disease Progression of HIV/SIV Infection.Viruses · 2022Pooled it
- Safety, Pharmacokinetics, and Pharmacodynamics of Single-Dose Programmed Cell Death Protein 1 Inhibitor, Budigalimab, in People With HIV-1 With Antiretroviral Therapy-Suppressed Viral Load.The Journal of infectious diseases · 2026Trial
- Anti-PD-L1 antibody ASC22 in combination with a histone deacetylase inhibitor chidamide as a "shock and kill" strategy for ART-free virological control: a phase II single-arm study.Signal transduction and targeted therapy · 2024Trial
- 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.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- In vivo effect of anti-PD-1 on HIV-specific CD8+T-cells in men with HIV.Nature communications · 2026Article
- The immunophenotype and proviral landscape of HIV-infected CD4 T cells during antiretroviral therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting rapidly cycling receptors CD2 and CD7 increases nanoparticle delivery to primary CD4Nature communications · 2026Article
- Network Pharmacology-Guided Identification ofInternational journal of molecular sciences · 2026Article
- Innate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapy.Nature medicine · 2026Article
- Virus-driven remodeling of the immune microenvironment and response to immune checkpoint inhibitors: the infection- immunity-cancer crosstalk.Frontiers in immunology · 2026Review
- PD-1/PD-L1 blockade in HIV-associated advanced lung cancer: from mechanisms to clinical practice.Frontiers in immunology · 2026Review
- Real-world efficacy and safety of PD-1 inhibitors in patients living with HIV and cancer: a retrospective cohort study.Frontiers in oncology · 2026Article
- Immune checkpoint inhibitors in infectious diseases: therapeutic reinvigoration, immunopathology, and precision targeting.Frontiers in immunology · 2026Review
- Impacts of immune checkpoint inhibitors use on the HIV reservoir are linked to provirus sequences but not integration sites.Scientific reports · 2025Article
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Pathogenic SIV infection is associated with acceleration of epigenetic age in rhesus macaques.The Journal of clinical investigation · 2025Article
- Effects of Oxygen Atom Position in Linear Side Chains of Ansellone Analogues on HIV Latency-Reversing Activity.ACS medicinal chemistry letters · 2025Article
- Tracking HIV persistence across T cell lineages during early ART-treated HIV-1-infection using a reservoir-marking humanized mouse model.Nature communications · 2025Article
- Latency Reversing Agents and the Road to an HIV CurePathogens (Basel, Switzerland) · 2025Review
- From natural defenders to therapeutic warriors: NK cells in HIV immunotherapy.Immunotherapy · 2025Review
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 9 institutions in 4 countries.
Funding
Abstract
objectiveIn HIV-infected individuals on antiretroviral therapy (ART), latent HIV is enriched in CD4 T cells expressing immune checkpoint molecules, in particular programmed cell death-1 (PD-1). We therefore assessed the effect of blocking PD-1 on latency, both in vitro and in vivo.
methodsHIV latency was established in vitro following coculture of resting CD4+ T cells with myeloid dendritic cells. Expression of PD-1 was quantified by flow cytometry, and latency assessed in sorted PD-1high and PD-1low/-nonproliferating CD4+ memory T cells. The role of PD-1 in the establishment of latency was determined by adding anti-PD-1 (pembrolizumab) to cocultures before and after infection. In addition, a single infusion of anti-PD-1 (nivolumab) was administered to an HIV-infected individual on ART with metastatic melanoma, and cell-associated HIV DNA and RNA, and plasma HIV RNA were quantified.
resultsHIV latency was significantly enriched in PD-1high compared with PD-1low/- nonproliferating, CD4 memory T cells. Sorting for an additional immune checkpoint molecule, T-cell immunoglobulin domain and mucin domain-3, in combination with PD-1, further enriched for latency. Blocking PD-1 prior to HIV infection, in vitro, resulted in a modest but significant decrease in latently infected cells in all donors (n = 6). The administration of anti-PD-1 to an HIV-infected individual on ART resulted in a significant increase in cell-associated HIV RNA in CD4 T cells, without significant changes in HIV DNA or plasma HIV RNA, consistent with reversal of HIV latency.
conclusionPD-1 contributes to the establishment and maintenance of HIV latency and should be explored as a target, in combination with other immune checkpoint molecules, to reverse latency.
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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.