ArticleThe Journal of clinical investigation2022
Combined noncanonical NF-κB agonism and targeted BET bromodomain inhibition reverse HIV latency ex vivo.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The trial behind it
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Empirical PK/PD Model for Differentiating Intrinsic Dosing Rules by Therapeutic Indication With Relevance for HIV-1 Latency Reversal.Clinical pharmacology and therapeutics · 2026Article
- A screen of chromatin-targeting compounds identifies TAF1 as a novel regulator of HIV latency.mBio · 2026Article
- Targeting NF-κB signaling for HIV latency reversal: Mechanisms, challenges, and therapeutic perspectives.Virus research · 2026Review
- From Epigenetic Regulation to Protein Degradation: Emerging Strategies for Anti-Infective Drug Discovery.International journal of molecular sciences · 2026Review
- Comparison of manual and automated ultrasensitive assays for residual HIV-1 in plasma from individuals on suppressive antiretroviral therapy.Journal of clinical microbiology · 2025Article
- HIV proviral transcription and infectivity are enhanced by neddylation.Journal of virology · 2025Article
- Combining BET inhibition with SMAC mimetics restricts tumor growth and triggers immune surveillance in preclinical cancer models.Cell reports. Medicine · 2025Article
- Using single cell technologies to understand HIV latency models.Current opinion in HIV and AIDS · 2025Review
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells.Journal of virology · 2025Article
- Integrator complex subunit 12 knockout overcomes a transcriptional block to HIV latency reversal.eLife · 2025Article
- The role of Tat in HIV latency and reactivation.Frontiers in immunology · 2025Review
- HIV-1 latency reversal agent boosting is not limited by opioid use.JCI insight · 2024Article
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.PLoS pathogens · 2024Article
- Nanoparticle delivery of Tat synergizes with classical latency reversal agents to express HIV antigen targets.Antimicrobial agents and chemotherapy · 2024Article
- HIV-1 latency reversal agent boosting is not limited by opioid use.medRxiv : the preprint server for health sciences · 2024Article
- The histone methyltransferase SETD2 regulates HIV expression and latency.PLoS pathogens · 2024Article
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.bioRxiv : the preprint server for biology · 2024Article
- Dynamic modulation of the non-canonical NF-κB signaling pathway for HIV shock and kill.Frontiers in cellular and infection microbiology · 2024Review
- A histone deacetylase network regulates epigenetic reprogramming and viral silencing in HIV-infected cells.Cell chemical biology · 2023Article
Corrections and comments
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Authors and funding
31 authors at 4 institutions in 2 countries.
Funding
Abstract
Latency reversal strategies for HIV cure using inhibitor of apoptosis protein (IAP) antagonists (IAPi) induce unprecedented levels of latent reservoir expression without immunotoxicity during suppressive antiretroviral therapy (ART). However, full targeting of the reservoir may require combinatorial approaches. A Jurkat latency model screen for IAPi combination partners demonstrated synergistic latency reversal with bromodomain (BD) and extraterminal domain protein inhibitors (BETi). Mechanistic investigations using CRISPR-CAS9 and single-cell RNA-Seq informed comprehensive ex vivo evaluations of IAPi plus pan-BET, bD-selective BET, or selective BET isoform targeting in CD4+ T cells from ART-suppressed donors. IAPi+BETi treatment resulted in striking induction of cell-associated HIV gag RNA, but lesser induction of fully elongated and tat-rev RNA compared with T cell activation-positive controls. IAPi+BETi resulted in HIV protein induction in bulk cultures of CD4+ T cells using an ultrasensitive p24 assay, but did not result in enhanced viral outgrowth frequency using a standard quantitative viral outgrowth assay. This study defines HIV transcriptional elongation and splicing as important barriers to latent HIV protein expression following latency reversal, delineates the roles of BET proteins and their BDs in HIV latency, and provides a rationale for exploration of IAPi+BETi in animal models of HIV 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.