ArticleThe Journal of clinical investigation2015
Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 286 papers, 1 of them a synthesis that pooled it.
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Who cites it
286 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Transcriptome profiles of latently- and reactivated HIV-1 infected primary CD4Frontiers in immunology · 2022Pooled it
- Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial.Clinical pharmacology and therapeutics · 2019Trial
- Granulocytic myeloid-derived suppressor cells sustain HIV reservoirs by inhibiting viral reactivation via arginase 1-mediated mechanisms.JCI insight · 2026Article
- PKC inhibitors reveal PKC isoforms involved in HIV latency reversal and immunomodulation.Journal of virology · 2026Article
- Effect of ligands and HIV latency-reversing agents on estrogen receptor α in CD4+ T cells.JCI insight · 2026Article
- Review
- Selective reactivation of latent HIV using CyclinT1-Tat-containing virus-like particles.Virology · 2026Article
- XQ2, a Novel Derivative of Resveratrol, Reactivates Latent HIV‑1 via the Activation of Positive Transcription Elongation Factor B.ACS omega · 2026Article
- Mechanisms of HIV Latency in Hematopoietic Progenitors: GFI1 as a Key Regulator.bioRxiv : the preprint server for biology · 2026Article
- Traditional Medicine Extracts ofInternational journal of molecular sciences · 2026Article
- Mechanistic insights and in vivo HIV suppression by the BRD4-targeting small molecule ZL0580.PLoS pathogens · 2026Article
- World free HIV: the novel therapeutic approaches for eliminating latent HIV infection.Virology journal · 2026Review
- Tools to Quantify and Characterize the Persistent Reservoir in People with HIV-1: Focus on Non-B Subtypes.Viruses · 2026Review
- Modulation of IRF7-driven transcription as a strategy to control HIV-1 latency.Frontiers in immunology · 2026Article
- Epigenetic regulation of HIV-1 transcription: insights into latency mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- The effect of combining HIV latency reversal with inhibition of phosphoinositide-3 kinases or B-cell lymphoma-2 on the HIV reservoir.PLoS pathogens · 2026Article
- Interleukin-2 is a potent latency reversal agent in people with treated HIV-1.Science advances · 2025Article
- Identification of inducible HIV reservoirs in tonsillar, intestinal and cervical tissue models of HIV latency.Nature communications · 2025Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- CD8medRxiv : the preprint server for health sciences · 2025Article
226 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs.
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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.