Impact of Myeloid Reservoirs in HIV Cure Trials

Curr HIV/AIDS Rep. 2019 Apr;16(2):129-140. doi: 10.1007/s11904-019-00438-5.

Abstract

Purpose of review: Gallant efforts are ongoing to achieve sustained antiretroviral therapy (ART)-free HIV remission in the HIV-infected person; however, most, if not all, current human clinical studies have primarily focused these efforts on targeting viral persistence in CD4 T cells in blood and tissue sanctuaries. The lack of myeloid centered HIV clinical trials, either as primary or secondary end points, has hindered our understanding of the contribution of myeloid cells in unsuccessful trials but may also guide successes in future HIV eradication clinical strategies.

Recent findings: Recent advances have highlighted the importance of myeloid reservoirs as sanctuaries of HIV persistence and therefore may partially be responsible for viral recrudescence following ART treatment interruption in several clinical trials where HIV was not detectable or recovered from CD4 T cells. Given these findings, novel innovative therapeutic approaches specifically focused on HIV clearance in myeloid cell populations need to be vigorously pursued if we are to achieve additional cases of sustained ART-free remission. This review will highlight new research efforts defining myeloid persistence and recent advances in HIV remission and cure trials that would be relevant in targeting this compartment and make an argument as to their clinical relevancy as we progress towards sustained ART-free HIV remission in all HIV-infected persons.

Keywords: Clinical trials; Cure; HIV; Macrophages; Microglia; Monocytes; Reservoirs.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anti-Retroviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology*
  • Clinical Trials as Topic
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects*
  • Humans
  • Myeloid Cells / drug effects
  • Myeloid Cells / virology*
  • Virus Latency / drug effects

Substances

  • Anti-Retroviral Agents