T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy

PLoS Pathog. 2021 Sep 23;17(9):e1009871. doi: 10.1371/journal.ppat.1009871. eCollection 2021 Sep.


HIV cerebrospinal fluid (CSF) escape, where HIV is suppressed in blood but detectable in CSF, occurs when HIV persists in the CNS despite antiretroviral therapy (ART). To determine the virus producing cell type and whether lowered CSF ART levels are responsible for CSF escape, we collected blood and CSF from 156 neurosymptomatic participants from Durban, South Africa. We observed that 28% of participants with an undetectable HIV blood viral load showed CSF escape. We detected host cell surface markers on the HIV envelope to determine the cellular source of HIV in participants on the first line regimen of efavirenz, emtricitabine, and tenofovir. We confirmed CD26 as a marker which could differentiate between T cells and macrophages and microglia, and quantified CD26 levels on the virion surface, comparing the result to virus from in vitro infected T cells or macrophages. The measured CD26 level was consistent with the presence of T cell produced virus. We found no significant differences in ART concentrations between CSF escape and fully suppressed individuals in CSF or blood, and did not observe a clear association with drug resistance mutations in CSF virus which would allow HIV to replicate. Hence, CSF HIV in the face of ART may at least partly originate in CD4+ T cell populations.

Publication types

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

MeSH terms

  • Adult
  • Alkynes / therapeutic use
  • Anti-HIV Agents / therapeutic use*
  • Benzoxazines / therapeutic use
  • Cyclopropanes / therapeutic use
  • Emtricitabine / therapeutic use
  • Female
  • HIV Infections / cerebrospinal fluid*
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1
  • Humans
  • Male
  • Middle Aged
  • T-Lymphocytes / virology*
  • Tenofovir / therapeutic use


  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Tenofovir
  • Emtricitabine
  • efavirenz