New latency-promoting agents for a block-and-lock functional cure strategy

Curr Opin HIV AIDS. 2024 May 1;19(3):95-101. doi: 10.1097/COH.0000000000000844. Epub 2024 Feb 27.

Abstract

Purpose of review: Currently, HIV-infected patients are treated with antiretroviral therapy. However, when the treatment is interrupted, viral rebound occurs from latently infected cells. Therefore, scientists aim to develop an HIV-1 cure which eradicates or permanently silences the latent reservoir.

Recent findings: Previously, scientists focused on the shock-and-kill cure strategy, which aims to eradicate the latent reservoir using latency-reactivating agents. Limited success shifts the interest towards the block-and-lock cure approach, which aims to achieve a functional cure by "blocking" HIV-1 transcription and "locking" the provirus in a deep latent state, resistant to treatment-interruption. In this strategy, latency promoting agents are used to induce transcriptional silencing and alter the epigenetics environment at the HIV promotor.

Summary: For the block-and-lock cure strategy to succeed more investigation into the transcriptional and epigenetic regulation of HIV-1 gene expression is necessary to design optimal latency-promoting agents. In this review, we will discuss the latency promoting agents that have been described in literature during the past 2 years (2022-2023).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes
  • Epigenesis, Genetic
  • HIV Infections*
  • Humans
  • Proviruses / genetics
  • Virus Activation* / genetics
  • Virus Latency / genetics