Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion.

Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet-Eomes- subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

Soluble plasma programmed death 1 (PD-1) and Tim-3 in primary HIV infection.

: Soluble forms of the coinhibitory receptors programmed death 1 (PD-1) and Tim-3 exist, but their relationship with T-cell surface expression remains unclear. When measured by an enzyme-linked immunosorbent assay in plasma, soluble PD-1, and soluble Tim-3 were elevated during primary HIV infection, decreased on antiretroviral therapy to levels found in controls, and correlated with cell surface expression. We conclude that soluble PD-1 and soluble Tim-3 are easy to measure biomarkers of immune exhaustion which potentially eliminate the need for flow cytometry.