Abstract
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.
Highlights
Human immunodeficiency virus (HIV) persists despite antiretroviral therapy (ART) in a reservoir of latently infected cells [1, 2], which is the focus of potentially curative interventions [3, 4]
We aimed to clarify this by using a longitudinally studied cohort of individuals treated during primary HIV infection (PHI) who were sampled before ART and again 1 year later once viremia was suppressed
HIV Reservoir Targeting with Early Antiretroviral Therapy (HEATHER) is a prospective observational cohort study of individuals who begin ART within 3 months of HIV diagnosis during PHI (West Midlands—South Birmingham Research Ethics Committee reference no. 14/WM/1104)
Summary
Human immunodeficiency virus (HIV) persists despite antiretroviral therapy (ART) in a reservoir of latently infected cells [1, 2], which is the focus of potentially curative interventions [3, 4]. There is much interest in which clinical, virological, or immunological parameters might determine the size of the reservoir. There are limited and conflicting data on which parameters predict reservoir size in treated HIV infection. Few studies have assessed immunological factors during early HIV infection that may determine subsequent reservoir size [5, 6, 21]. We aimed to clarify this by using a longitudinally studied cohort of individuals treated during primary HIV infection (PHI) who were sampled before ART and again 1 year later once viremia was suppressed
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