The aim of this study was to assess immune activation in various organs by longitudinally measuring changes in glucose metabolism associated with initiation and interruption of combination antiretroviral therapy (cART) in SIV-infected macaques. We also assessed the associations of various markers of disease activity with tissue metabolic activity.
Whole body 18F-Fluorodeoxyglucose (FDG) PET-imaging was obtained on seven SIV-infected macaques at various time points before and after initiation (n=5)/interruption (n=5) of cART, up to 9 months after treatment modification. SUVmax values were measured in the spleen, axillary and inguinal lymph nodes (axLNs, ingLNs), liver and bone marrow (BM). Univariate and multivariate mixed-effect linear regression models estimated the associations of FDG uptake with peripheral blood CD4 cell counts, plasma viral load (VL) and serum cytokine levels (IL-1ra, IL2, IL-8, IL-15 and MCP-1). We used the Spearman rank statistic to correlate BM SUVmax to SUVmax values of the rest of the organs, using the bootstrap to account for repeated measures.
FDG uptake showed concomitant changes with peripheral markers of disease after initiation/interruption (Fig. 1). In the univariate analyses, except for the liver, a significant inverse association of FDG uptake in each organ was found with CD4 counts (P<0.05) and direct association with plasma VL (P≤0.001). In the multivariate analyses, only plasma VL remained statistically significantly associated with the FDG-uptake in the lymphoid organs (P<0.01 for axLNs, ingLNs and spleen) and the BM (P<0.05). Spearman rank correlations between BM SUVmax and SUVmax of the lymphoid organs (spleen, AxLNs and IngLNs) were significant (P<0.001).There were no statistically significant correlations detected between FDG uptake and serum cytokines.
Changes in immune activation as measured by glucose metabolism (FDG PET) following initiation/interruption of cART were observed in the spleen and clusters of lymph nodes, as previously reported by other groups. A new finding in this study however is that a similar pattern is also observed in the BM, a primary lymphoid organ. The plasma VL appears to be the primary factor affecting FDG uptake in these lymphoid organs, suggesting an inflammatory/hematopoietic reaction to peripheral viral rebound or control.