The HIV reservoir persists even in the setting of effectively treated and suppressed HIV infection. Preclinical models strongly implicate lymphoid structures as a major reservoir. 18F-fluorodeoxyglucose (FDG) PET/CT is an imaging modality that quantifies inflammation in these tissues. We assessed the association between lymph node inflammation and the size of the reservoir.
A total of 64 participants, ages 40 and older, were recruited from the SCOPE cohort. There were 45 HIV-infected participants and 19 controls that were matched by age, gender, Framingham Score, and race. Thirty-four of those with HIV were treated and suppressed and 7 were elite controllers. Participants underwent 18FDG-PET/CT imaging after an overnight fast and FDG uptake in the axillary lymph nodes (LN) was assessed as a mean standardized uptake value (SUV). A target to background ratio (TBR) for LN was generated by dividing LN SUV by blood background SUV. Viral persistence was measured using frequency of cells harboring integrated HIV DNA in CD4+ T cells.
Lymph node inflammation was lower in HIV-uninfected controls (TBR: 0.97 (0.84-1.37)) compared to treated and suppressed individuals (1.39 (1.01-2.23) p=0.02) and elite controllers (1.36 (0.92-2.19), p=0.07) as shown in Figure 1. Higher inflammation in the lymph nodes was associated with higher HIV RNA viral load (r=0.53, p<0.001), even after correcting for antiretroviral therapy, CD4 count, or history of opportunistic infections (p=0.006). Additionally, higher lymph node inflammation was associated with markers of viral persistence among the elite controllers (Integrated HIV DNA, r=0.78, p=0.039), but not the treated suppressed (r=0.051, p=0.794). Among those on effective ART, lymph node inflammation was associated with higher markers of CD4+ T-cell activation (HLADR+CD38+ cells: r=0.53, p=0.003) and higher levels of IL-6 (r=0.43, 0=0.02).
Lymph node activity as assessed by FDG-PET/CT was higher among HIV-infected individuals compared to controls and was associated with markers of viral persistence and inflammation. Our findings support the hypothesis that among elite controllers, HIV serves as the main driver of inflammation as opposed to those on ART. FDG PET/CT imaging of the axillary lymph nodes may provide a method to non-invasively measure reservoirs of viral persistence in HIV and assess response to different antiretroviral therapies or anti-inflammatory interventions.