ArticleCellular and molecular bioengineering2014
Quantitative evaluation and optimization of co-drugging to improve anti-HIV latency therapy.
Article in Cellular and molecular bioengineering, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- A transcriptional cycling model recapitulates chromatin-dependent features of noisy inducible transcription.PLoS computational biology · 2022Article
- Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARS-CoV-2 infection.PLoS computational biology · 2020Article
- Diversity of small molecule HIV-1 latency reversing agents identified in low- and high-throughput small molecule screens.Medicinal research reviews · 2020Review
- Hybrid nanocarriers incorporating mechanistically distinct drugs for lymphatic CD4Science advances · 2019Article
- A New Quinoline BRD4 Inhibitor Targets a Distinct Latent HIV-1 Reservoir for Reactivation from Other "Shock" Drugs.Journal of virology · 2018Article
- Trade-off between synergy and efficacy in combinations of HIV-1 latency-reversing agents.PLoS computational biology · 2018Article
- Systems analysis of latent HIV reversal reveals altered stress kinase signaling and increased cell death in infected T cells.Scientific reports · 2017Article
- Distinct promoter activation mechanisms modulate noise-driven HIV gene expression.Scientific reports · 2015Article
- BIRC2/cIAP1 Is a Negative Regulator of HIV-1 Transcription and Can Be Targeted by Smac Mimetics to Promote Reversal of Viral Latency.Cell host & microbe · 2015Article
- A passive-flow microfluidic device for imaging latent HIV activation dynamics in single T cells.Integrative biology : quantitative biosciences from nano to macro · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Human immunodeficiency virus 1 (HIV) latency remains a significant obstacle to curing infected patients. One promising therapeutic strategy is to purge the latent cellular reservoir by activating latent HIV with latency-reversing agents (LRAs). In some cases, co-drugging with multiple LRAs is necessary to activate latent infections, but few studies have established quantitative criteria for determining when co-drugging is required. Here we systematically quantified drug interactions between histone deacetylase inhibitors and transcriptional activators of HIV and found that the need for co-drugging is determined by the proximity of latent infections to the chromatin-regulated viral gene activation threshold at the viral promoter. Our results suggest two classes of latent viral integrations: those far from the activation threshold that benefit from co-drugging, and those close to the threshold that are efficiently activated by a single drug. Using a primary T cell model of latency, we further demonstrated that the requirement for co-drugging was donor dependent, suggesting that the host may set the level of repression of latent infections. Finally, we showed that single drug or co-drugging doses could be optimized, via repeat stimulations, to minimize unwanted side effects while maintaining robust viral activation. Our results motivate further study of patient-specific latency-reversing strategies.
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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.