Background:
Non-invasive tools that can test the hypothesis that abnormal T cell activation in various tissues differs across HIV-1 disease states are needed. We used [18F]F-AraG, a small-molecule PET tracer highly specific for activated T cells (CD8>CD4), to compare whole-body T cell activation states in people with HIV (PWH) on and off ART, and experiencing post-intervention control (PIC), compared to uninfected control participants.
Methods:
[18F]F-AraG (~5mCi) was administer i.v. to13 PWH (12 male, one transgender female; 8 on ART, 2 viremic, 3 PIC following combination immunotherapy) and 6 uninfected volunteers [3 male, 3 female]) followed by whole-body PET-MR imaging. Maximum and mean standardized uptake values (SUVmax/mean) were calculated for regions of interest (ROI) and compared across cohorts using non-parametric tests adjusted for multiple comparisons.
Results:
We observed significantly higher [18F]F-AraG SUVmean and SUVmax in many tissues (nasal turbinates, axial bone marrow, distal spinal cord/cauda equina, lung parenchyma, pulmonary artery, and rectal wall) in PWH comparted to uninfected controls (all P<0.05; Fig 1). Elevated T cell activation was evident even among those on ART (VL<40 c/mL) in these ROI with the exception of lung tissue. Interestingly, tracer uptake was significantly lower in inguinal lymph nodes from all PWH, PWH on ART, and PTC, compared to uninfected controls (all P<0.02). PWH experiencing PIC had significantly higher SUVmean/max in pulmonary artery, axial marrow and rectal wall (SUVmean) compared to uninfected controls, but not in lungs or nasal turbinates. There were no significant differences in tracer uptake in male versus female control participants in any ROI and analyses of all PWH excluding female controls yielded similar results.
Conclusions:
This study is the first to show persistent T cell activation in bone marrow, pulmonary artery, and nasal and gut tissue across a range of HIV-1 disease states using non-invasive PET-MR imaging. Interestingly, T cell activation in lung parenchyma appears to be driven by viremic PWH, and all PWH had lower T cell activation in inguinal lymph nodes compared to uninfected controls, regardless of disease phenotype. We previously observed high uptake of a HIV gp120-specific bnAb PET tracer in inguinal lymph nodes from viremic and ART-suppressed PWH suggesting that combinations of non-invasive imaging tools may play an important role in determining the interplay between host immune responses and viral persistence.
