Differences in neuroinflammation in people who started antiretroviral treatment during primary versus chronic HIV infection: an 18kDa Translocator protein (TSPO) positron emission tomography (PET) study

Abstract

Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, using translocator protein (TSPO) [¹¹C]PBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population. This was a cross-sectional, observational study. All participants underwent [¹¹C]PBR28 PET-CT neuroimaging. Using a two-tissue compartment model, total volume of distribution (V_T) and distribution volume ratios (DVR) using cortical grey matter as a pseudo-reference region at 20 regions of interest (ROIs) were calculated. Differences in V_T and DVR were compared between groups using the Kruskall-Wallis test. Seventeen neuro-asymptomatic male PWH on ART (9 aPWH, 8 cPWH) and 8 male control participants (CPs) were included. Median (interquartile range, IQR) age was 40 (30, 46), 44 (41, 47) and 21 (20, 25) years in aPWH, cPWH and CPs, respectively. Median (IQR) CD4 (cells/µL) and CD4:CD8 were 687 (652, 1014) and 1.37 (1.24, 1.42), and 700 (500, 720) and 0.67 (0.64, 0.82) in aPWH and cPWH, respectively. Overall, no significant difference in V_T and DVR were observed between the three groups at any ROIs. cPWH demonstrated a trend towards higher mean V_T compared with aPWH and CPs at most ROIs. No significant differences in neuroinflammation, using [¹¹C]PBR28 binding as a proxy, were identified between cPWH, aPWH and CPs. A trend towards lower absolute [¹¹C]PBR28 binding was seen amongst aPWH and CPs, suggesting early ART may mitigate neuroinflammation.