Abstract Body

Background:

Mechanisms of HIV persistence in anatomic compartments remain poorly understood. Positron Emission Tomography (PET) is a non-invasive technique that may provide insights to the spatial distribution and microenvironment of HIV persistence and identify sites for tissue sampling. Early 18F-fluorodeoxyglucose PET (FDG-PET) techniques did not detect elevated metabolic activity during long-term antiretroviral therapy (ART), though increased metabolic activity was observed with rebound viremia. To investigate whether new technologically advanced PET imaging with improved resolution detects metabolic activity in lymphoid tissues during long-term ART, we used FDG-PET co-registered with computed tomography (CT) followed by fusion guided lymph node biopsy to obtain samples for characterization.

Methods:

Participants recruited through NIH study NCT05419024 (Imaging and Biopsy of HIV-Infected Individuals Undergoing Analytic Treatment Interruption (ATI)) underwent FDG-PET-CT and FDG uptake was quantified as standardized uptake value (SUV; FDG uptake normalized to injected activity/weight). Tissue was sampled with ultrasound fusion guidance and aspiration. HIV RNA in plasma and cell-associated (CA) HIV DNA and RNA in cells from blood and lymphoid tissue were quantified by single copy assays (Somsouk et al., 2014).

Results:

Study participants (N=2; HIV RNA <50 copies/ml plasma for >3 y, CD4 562-590) underwent imaging and guided biopsy. Imaging noted lymph nodes were all ≤ 1cm diameter; although most nodes had minimal FDG signal, increased uptake was detected in c. 3-10 lymph nodes in both participants (SUVmax 1.14 – 6.4), indicating increased metabolic activity was present in these tissues. Metabolically active nodes were present in mediastinal, axillary and inguinal distributions. Nodes accessible to fusion guided sampling yielded 104-105 cells. Levels of HIV DNA in biopsies (610-900 HIV DNA copies/1e6 cells) were c. 5 -15-fold higher than levels in peripheral blood mononuclear cells (PBMC). HIV RNA was quantifiable in both nodal tissue and PBMC; levels of HIV RNA/DNA (0.4-1.2 RNA copies/DNA copy) were comparable in blood and nodal sampling.

Conclusions:

New non-invasive imaging approaches identify increased metabolic activity in subsets of lymph nodes during long term ART, and directed biopsy recovers sufficient HIV DNA and RNA for analysis even in nodes < 1cm size. Image guided approaches will advance understanding of HIV persistence in tissues.