CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Conclusions: Inducible virion production from resting CD4+ T cells ex vivo is strongly associated with the number of HIV-infected cells and the basal level of HIV-1 RNA transcription in isolated PBMC. These data indicate that simple, high-throughput and relatively inexpensive measures of cellular HIV-1 RNA and DNA can be used to estimate the size of the inducible reservoir in patients on suppressive ART. These approaches could also be useful in assessing the effectiveness of interventions targeting the latent HIV reservoir.

343 FDG PET/CT Imaging of Lymph Nodes As a Measure of the HIV Reservoir in Humans

Priscilla Hsue 1 ; RichardTakx 2 ; Amorina Ishai 2 ; Irini Sereti 3 ; Remi Fromentin 4 ; Nicolas Chomont 4 ; Sophia Hur 1 ; Peter Ganz 1 ; Steven G. Deeks 1 ; AhmedTawakol 2 1 Univ of California San Francisco, San Francisco, CA, USA; 2 Massachusetts General Hosp, Boston, MA, USA; 3 NIH, Bethesda, MD, USA; 4 Univ of Montreal, Montreal, QC, Canada Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Poster Abstracts

344

Activation of Nasopharynx-Associated Lymphoid Tissue in HIV Infection Danny Li 1 ; RichardTakx 2 ; Amorina Ishai 2 ; Remi Fromentin 3 ; Irini Sereti 4 ; Nicolas Chomont 4 ; Sophia Hur 1 ; Steven G. Deeks 1 ; Priscilla Hsue 1 ; AhmedTawakol 2 1 Univ of California San Francisco, San Francisco, CA, USA; 2 Massachusetts General Hosp, Boston, MA, USA; 3 Univ of Montreal, Montreal, QC, Canada; 4 NIH, Bethesda, MD, USA Background: Nasopharynx-associated lymphoid tissue (NALT) plays an important role in stimulating immune responses against alimentary and airborne antigens. Tissue- resident inflammatory cells are metabolically active and can be quantified using an infusion of 18F-fluorodeoxyglucose (FDG) followed by a PET scan to identify heightened inflammation. We compared NALT in HIV-infected individuals and matched HIV-negative controls and assessed the association between NALT and inflammatory markers, markers of immune activation, and size of the HIV reservoir.

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CROI 2016

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