Persistently 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.
Abstract Background The main cause of the persistently high levels of immune activation in HIV positive patients undergoing suppressive chronic cART is still unknown. Previous findings have suggested a link between ongoing residual viral replication originating from the HIV reservoir and the immune activation levels. However, there is no clear evidence of this assumption. The aim of this study was to investigate the correlation between the reservoir and the levels of immune activation in chronic patients under fully suppressive cART. Methods We conducted a prospective longitudinal study in a cohort of HIV positive patients undergoing cART for more than 5 years without any documented blips. We quantified the HIV proviral DNA and the 2-LTR circles loads from PBMCs, the levels of immune activation and proliferation markers of T-cells (CD38+, Ki-67+), and the levels of plasmatic IL-7 at enrollment and 1-year of follow-up. Correlation analysis and group comparison were performed. Results 29 participants with a median of 8 years (IQR, 6.9-9.4) under suppressive cART were enrolled and successfully followed at 1 year. In this cohort, we found higher levels of CD8+ T-cell activation (CD38+) after 1-year (P = .000). There was a very weak correlation between the levels of immune activation and the proviral DNA of CD4+ T-cell and CD8+ T-cell. The levels of Ki-67+ T-cells declined on time without significant differences, and there was no significant correlation with the proportion of activated T-cells. The plasmatic levels of IL-7 decreased at the follow-up observation (P = .094), but there was no correlation with the levels of immune activation either. Conclusions We found a weak correlation of the levels of CD4+ and CD8+ 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 subjects under chronic suppressive cART. More importantly, we highlight the relevance of decreasing T-cell activation in chronic patients to lower the risk of morbidity and early mortality by investigating other activation pathways in specifically chronic phases.