Persistent high levels of immune activation and correlations with HIV-1 proviral DNA and 2-LTR circle loads in a cohort of Mexican individuals following long-term and fully suppressive treatment

Abstract

Objectives: This study investigated the correlations between the human immunodeficiency virus type 1 (HIV-1) reservoir and immune activation levels in chronic patients under fully suppressive antiretroviral therapy (ART). Methods: We quantified the HIV-1 proviral DNA and 2-long terminal repeat (2-LTR) circle loads from peripheral blood mononuclear cells, the levels of CD38+ and Ki-67+ T-cells, and the levels of interleukin 7 (IL-7) in a cohort of patients with more than 5 years of ART at enrollment and after 1 year. Results: Among 29 participants with a median of 8 years (inter-quartile range, 6.9–9.4) under suppressive ART, we found higher levels of CD8+ CD38+ T-cells after 1 year (P = .000). We determined weak and statistically non-significant correlations between the levels of immune activation and the proviral DNA loads in CD4+ and CD8+ T-cells. Ki-67+ T-cells declined but not significantly and there was no significant correlation with the proportion of CD38+. Plasmatic IL-7 did not consistently correlated with the CD38+ and Ki-67+ T-cells. Conclusions: We found weak but statistically non-significant correlations between the levels of T-cell activation and the proviral DNA and 2-LTR circle loads. These results suggest that mechanisms other than viral replication drive chronic versus early immune activation in the long term.

Keywords

• Immune activation
• Reservoir
• Proviral DNA
• 2-LTR circles
• IL-7
• Chronic ART