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PBR28 PET IMAGING IN PEOPLE WHO STARTED
ART DURING ACUTE VERSUS CHRONIC HIV INFECTION
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CROI 2022 Feb 11-16
Jasmini Alagaratnam1, Jaime Vera, Zhen Fan, John Thornhill, Jonathan
Underwood, David Owen, Paul Edison, Sarah Fidler and Alan Winston
program abstract
Background: Despite antiretroviral therapy (ART), persistent immune activation is described in people-with-HIV (PWH). Using translocator protein (TSPO) PET imaging, neuroinflammation is described in PWH on ART. Early ART initiation is associated with reduced markers of inflammation. We hypothesised that neuroinflammation, measured using TSPO [11C]PBR28, would be lower in PWH who initiated ART during acute (aPWH) versus chronic HIV infection (cPWH). We also investigate [11C]PBR28 binding normalised to reference regions previously used in TSPO studies.
Methods: Twenty TSPO high-affinity binders, neuro-asymptomatic PWH on virologically suppressive ART (9 aPWH, 11 cPWH) and 15 control participants underwent [11C]PBR28 PET scanning. Using a two-tissue compartment model, distribution volume ratios (DVR) were calculated using the reference regions: cortical grey matter (GM), total GM, cerebellum, cerebellar GM and cerebral white matter, at 20 regions of interest (ROIs). Differences in DVRs were compared between the groups using Kruskall-Wallis and Mann-Whitney U-tests.
Results: All PWH were male with median (interquartile range, IQR) age 40 (30, 46) and 45 (43, 52) years in the aPWH and cPWH, respectively, while 4/15 controls were female with median (IQR) age 26 (20, 59) years. Median (IQR) CD4 count (cells/μL) and CD4:CD8 were 687 (652, 1014) and 1.4 (1.2, 1.4), and 671 (470, 810) and 0.7 (0.6, 0.8) in aPWH and cPWH, respectively. Significant differences (p<0.05) in DVR were observed between cPWH and control participants and between cPWH and aPWH at certain ROIs (Figure 1). No differences in DVRs at any ROIs were noted between aPWH and controls. When utilising the cerebellum and cerebellar GM as reference regions, the greatest differences in DVR between the groups were observed and cPWH had lower binding at several ROIs.
Conclusion: Significant differences in [11C]PBR28 binding were identified between cPWH and control participants whereas differences between aPWH versus cPWH were observed less frequently. Neuroinflammation in aPWH and controls were similar, suggesting early ART initiation may mitigate neuroinflammatory responses. Cerebral [11C]PBR28 DVR binding is dependent on the reference region used and was lower in cPWH in several anatomical locations. We hypothesise this may be due to cerebral volume loss or regional neuroinflammation in cPWH. Urgent consensus is required on the optimal reference region in TSPO studies in PWH.
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