Background
Increased immune activation during antiretroviral therapy (ART) is associated with morbidity and mortality in persons with HIV (PWH). Mechanisms of elevated inflammation are uncertain but may include expression from HIV proviruses or dysregulated immune responses. Immune activation is often associated with increased metabolic activity in lymphoid organs, and can be detected non-invasively by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Early PET studies did not detect increased metabolic activity in lymphoid tissues during ART. We investigated whether new, more sensitive FDG PET/CT approaches detect metabolically active lymphoid tissues during ART.
Methods
Otherwise healthy PWH on ART with HIV RNA<20 c/ml for >3 years (y) underwent research time-of-flight FDG PET/CT using the Siemens Biograph mCT. Scans were analyzed using Medical Image Merge Software (MIM®). Cervical, mediastinal, axillary, and inguinal lymph nodes were identified manually and verified by a board-certified Nuclear Medicine radiologist. Metabolic activity in lymph nodes was quantified as standardized uptake value (SUV). Numbers of lymph nodes with 18F exceeding established threshold for normal uptake (SUVmax > 2.5) were quantified; SUVmax, total lesion glycolysis, and total lymph node volume were analyzed with descriptive parametric statistics.
Results
Four males (mean age 62, range 42-83) y, undergoing ART for mean 21 (range 5-31) y, with median CD4 560 (range 402-590) cells/µL), underwent PET/CT; 7-32 nodes/PWH were evaluated. Metabolically active lymph nodes were identified in cervical, mediastinal, axillary, and/or inguinal regions in all participants; ≥ 3 lymph nodes with SUVmax > 2.5 were identified per PWH. Mean SUVmax was 3.8 (0.9-11.2). Total lymph node volume was similar for nodes with SUVmax<2.5 [0.21 (0.004-0.9) mL] and SUVmax>2.5 [0.25 (0.01-1.13) mL] (p=0.2091). Mean total lesion glycolysis was lower for nodes with SUVmax<2.5 [0.26 (0.01-1.3)] vs SUVmax>2.5 [0.73 (0.03-3.4)] (p=0.0015). Anatomic locations of elevated activity varied among participants; no clinical or laboratory findings explained the abnormal uptake.
Conclusions
New PET imaging approaches localize elevated metabolic activity in lymph nodes of otherwise healthy PWH on long-term ART. While uptake varies significantly, nodal volumes do not. Non-invasive functional imaging will facilitate targeted evaluation of lymphoid tissues to determine mechanisms of immune activation during ART.