HIV reservoir size is determined prior to ART initiation and linked to CD8 T cell activation and memory expansion
Martin G., Pace M., Shearer F., Zilber E., Hurst J., Meyerowitz J., Thornhill J., Lwanga J., Brown H., Robinson N., Hopkins E., Olejniczak N., Nwokolo N., Fox J., Fidler S., Willberg C., Frater J., on behalf of the CHERUB investigators None.
Abstract Initiation of antiretroviral therapy (ART) in early compared with chronic HIV infection is associated with a smaller HIV reservoir. This longitudinal analysis of 63 individuals who commenced ART during primary HIV infection (PHI) investigates which pre-and post-therapy factors associate most closely with reservoir size (HIV DNA) following treatment initiation during PHI. The best predictor of reservoir size at one-year was pre-ART HIV DNA which was in turn significantly associated with CD8 memory differentiation (effector memory, naïve and T-bet neg Eomes neg subsets), CD8 T cell activation (CD38 expression) and PD-1 and Tim-3 expression on memory CD4 T cells. No associations were found for any immunological variables following one-year of ART. HIV reservoir size is determined around the time of ART initiation in individuals treated during PHI. CD8 T cell activation and memory expansion are linked to HIV reservoir size, suggesting the importance of the initial host-viral interplay in eventual reservoir size.