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Updated: May 15, 2026
07:18
High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Targeting HIV latency: pharmacologic strategies toward eradication
Sifei Xing1, Robert F Siliciano
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Drug Discovery Today
|December 29, 2012
Summary
The latent HIV-1 reservoir in CD4(+) T cells hinders eradication. This review explores small molecule latency-reversing agents that reactivate the reservoir by targeting transcriptional suppression mechanisms.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- The persistent latent reservoir of HIV-1 in resting CD4(+) T cells is a significant obstacle to complete viral eradication, despite effective antiretroviral therapies.
- Highly active antiretroviral therapy (HAART) suppresses plasma HIV-1 but does not eliminate the latent viral reservoir.
- HIV-1 latency is maintained by mechanisms including transcriptional suppression, epigenetic modifications (histone deacetylation, methylation, DNA methylation), and cytoplasmic sequestration of transcription factors.
Purpose of the Study:
- To review current pharmacological strategies for HIV-1 eradication.
- To focus on small molecule latency-reversing agents (LRAs) for reactivating the latent HIV-1 reservoir.
- To discuss the mechanisms, advantages, and limitations of these LRAs.
Main Methods:
- Literature review of pharmacological approaches for HIV-1 eradication.
- Analysis of small molecule LRAs targeting mechanisms of HIV-1 latency.
- Discussion of the molecular mechanisms underlying LRA efficacy and challenges.
Main Results:
- Multiple epigenetic and transcriptional mechanisms contribute to maintaining HIV-1 latency.
- Small molecule LRAs show potential for reactivating the latent reservoir.
- Various LRAs have demonstrated different efficacies and associated challenges.
Conclusions:
- Reactivation of the latent HIV-1 reservoir is a key strategy for eradication.
- Small molecule LRAs offer promising avenues for targeting latency.
- Further research is needed to optimize LRA efficacy and overcome limitations for potential clinical application.
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