Molecular Mechanisms Controlling HIV Transcription and Latency – Implications for Therapeutic Viral Reactivation

Abstract

Persistence of transcriptionally silent replication competent HIV-1 is a major barrier to clearance of the virus from patients; current combinatorial antiretroviral therapies are successful in abrogating active viral replication, but are unable to eradicate latent HIV-1. A “shock and kill” strategy has been proposed as a curative approach in which latent vi‐ rus is activated and infected cells are removed by immune clearance, while new rounds of infection are prevented by antiretroviral therapy. Much effort has been put toward un‐ derstanding the molecular mechanisms maintaining HIV latency and the nature of reser‐ voirs, to provide novel therapeutic targets. This has led to the development of latency reversal agents (LRAs), some of which are undergoing clinical trials. Targeting multiple mechanisms underlying HIV latency via a combination of LRAs is likely to result in more potent activation of the latent reservoir. Therefore, novel as well as synergistic combina‐ tions of therapeutic molecules are required to accomplish more potent latency reversal.