Persistent high levels of immune activation and their correlation with the HIV-1 proviral DNA and 2-LTR circles loads, in a cohort of Mexican individuals following long-term and fully suppressive treatment

Int J Infect Dis. 2020 Nov:100:184-192. doi: 10.1016/j.ijid.2020.08.044. Epub 2020 Aug 20.

Abstract

Objectives: The aim of this study was to investigate the correlation between the HIV-1 reservoir and the levels of immune activation in chronic patients under fully suppressive cART.

Methods: We quantified the HIV proviral DNA and 2-LTR circles loads from PBMCs, the levels of CD38+ and Ki-67+ T-cells, and the levels of IL-7 in a cohort of patients with more than 5 years of ART at enrollment and after 1 year.

Results: In 29 participants with a median of 8 years (IQR, 6.9-9.4) under suppressive cART we found higher levels of CD8+ CD38+ T-cells after 1-year (P = .000). There was a non-statistically significant poor correlation between the levels of immune activation and the proviral DNA of CD4+ and CD8+ T-cells. Ki-67+ T-cells declined without significant differences, and there was no significant correlation with the proportion of CD38+. IL-7 decreased at the follow-up observation (P = .094), but there was no correlation with the levels of CD38+ and Ki-67+ T-cells.

Conclusions: We found a weak but non-statistically significant correlation of the levels of T-cell activation with the proviral DNA and 2-LTR circles. This suggests the likely occurrence of further mechanisms driving chronic versus early immune activation other than viral replication by itself in chronic patients.

Keywords: 2-LTR circles; IL-7; Immune activation; chronic cART; proviral DNA; reservoir.

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • Cohort Studies
  • DNA, Viral / genetics*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Humans
  • Interleukin-7 / immunology
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Prospective Studies
  • Terminal Repeat Sequences / genetics*
  • Viral Load
  • Virus Replication

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • IL7 protein, human
  • Interleukin-7