Getting the "Kill" into "Shock and Kill": Strategies to Eliminate Latent HIV

Cell Host Microbe. 2018 Jan 10;23(1):14-26. doi: 10.1016/j.chom.2017.12.004.


Despite the success of antiretroviral therapy (ART), there is currently no HIV cure and treatment is life long. HIV persists during ART due to long-lived and proliferating latently infected CD4+ T cells. One strategy to eliminate latency is to activate virus production using latency reversing agents (LRAs) with the goal of triggering cell death through virus-induced cytolysis or immune-mediated clearance. However, multiple studies have demonstrated that activation of viral transcription alone is insufficient to induce cell death and some LRAs may counteract cell death by promoting cell survival. Here, we review new approaches to induce death of latently infected cells through apoptosis and inhibition of pathways critical for cell survival, which are often hijacked by HIV proteins. Given advances in the commercial development of compounds that induce apoptosis in cancer chemotherapy, these agents could move rapidly into clinical trials, either alone or in combination with LRAs, to eliminate latent HIV infection.

Keywords: Akt inhibitors; Bcl-2 antagonists; HIV cure; HIV latency; PI3K inhibitors; RIG-I inducers; Smac mimetics; XIAP inhibitors; apoptosis; latency reversing agents; pro-apoptotic drugs; shock and kill.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Bryostatins / therapeutic use
  • CD4-Positive T-Lymphocytes / virology
  • Depsipeptides / therapeutic use
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • Humans
  • Hydroxamic Acids / therapeutic use
  • Indoles / therapeutic use
  • Panobinostat
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Virus Activation / drug effects*
  • Virus Latency / drug effects*
  • Vorinostat


  • Anti-HIV Agents
  • Bryostatins
  • Depsipeptides
  • Hydroxamic Acids
  • Indoles
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Vorinostat
  • Panobinostat
  • romidepsin