CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

238 18F-FDG-PET/CT ABNORMALITIES ARE ASSOCIATED WITH HIGHER RISK OF IRIS IN HIV

Dima A. Hammoud 1 , Georgios Z. Papadakis 1 , Afroditi Boulougoura 2 , Virginia Sheikh 3 , Lori E. Dodd 4 , Jing Wang 5 , Angela Kibiy 6 , JoAnn Mican 2 , Corina Millo 1 , Irini Sereti 2 1 NIH, Bethesda, MD, USA, 2 NIAID, Bethesda, MD, USA, 3 FDA, Silver Spring, MD, USA, 4 NIAIDs, Rockville, MD, USA, 5 Leidos Biomed Rsr, Rockville, MD, USA, 6 Leidos Biomed Rsr, Bethesda, MD, USA Background: Immune reconstitution inflammatory syndrome (IRIS) in HIV infected patients represents a paradoxical immune response after initiation of antiretroviral therapy (ART). The pathogenesis and diagnostic criteria of IRIS remain elusive. We hypothesized that 18F-FDG-PET/CT scan could assess the acute effects of ART initiation on HIV+ patients and potentially assist in identifying those at high risk for IRIS. Methods: 31 HIV+/ART-naïve patients with CD4 <100 cells were included in this prospective study and underwent 18F-FDG-PET/CT scans pre-ART (baseline) and 4-8 weeks after ART initiation. Regions of interest were delineated over liver, spleen, bone marrow (BM), axillary and inguinal lymph nodes (LN). SUVmean, SUVmax between baseline and post-ART among various groups were compared (Paired T-test). The lesion load was assessed as areas of non-physiologic FDG uptake (infectious/neoplastic) throughout the body with SUV > 4; Total glycolytic activity (TGA) values were obtained. Baseline TGA values and change from baseline values (between follow-up and baseline scans) were then compared between groups (Wilcoxon rank sum statistics). Results: The median (IQR) age of the patients was 36 (32,39) and the median (IQR) hemoglobin (Hb), CD4+ T cells and HIV viral load (VL) were 10.1 (9.3, 11.5) g/dL, 25 (11, 36) cells/uL and 5.36 (4.94, 5.86) log10 copies/mL respectively. 11 patients eventually developed IRIS (6 mycobacterial IRIS-M. tuberculosis or M. avium complex). Baseline HIV VL was significantly higher in IRIS compared to non-IRIS. Mycobacterial IRIS patients had higher HIV VL and d-dimer levels, and lower Hb level than the rest of the cohort (p values 0.006, 0.038, 0.031 respectively). At baseline, lesion load TGA and volume were significantly higher in IRIS vs non-IRIS (~3X) and even more impressively in mycobacterial-IRIS vs the rest of the cohort (~10X) (table 1). Post-ART, BM and spleen SUVmean decreased in non-IRIS group by 17.8% (p=0.004) and 6.3% (p=0.013) respectively, but not significantly in the non-IRIS group. At baseline, HIV VL positively correlated with SUVmean in the spleen (r=0.48, p=0.01) and inguinal LN (r=0.49, p=0.01). Conclusion: Higher lesion load TGA/volume at baseline could indicate increased risk of developing IRIS after ART initiation especially in mycobacterial/HIV co-infected patients. In addition, acute decrease in metabolic activity in spleen and BM in non-IRIS patients post-ART suggests an important role of these sites as tissue viral reservoirs.

Poster and Themed Discussion Abstracts

239 MAIT CELLS, MICROBIAL TRANSLOCATION AND THE MICROBIOME IN HIV/HCV CHRONIC INFECTIONS Esther Merlini 1 , Maddalena Cerrone 1 , Bonnie van Wilgenburg 2 , Leo Swadling 2 , Camilla Tincati 1 , Elvira S. Cannizzo 1 , Antonella d’Arminio Monforte 1 , Paul Klenerman 2 , Giulia Marchetti 1 1 Univ of Milan, Milan, Italy, 2 Univ of Oxford, Oxford, UK Background: Both HIV and HCV infections feature increased microbial translocation (MT) and gut dysbiosis that hamper immune homeostasis and disease outcome. Given their commitment to antimicrobial mucosal immunity, we investigated mucosal-associated invariant T (MAIT) cells frequency/function and association with MT/microbiome in HIV, HCV mono- and co-infection. Methods: We enrolled 54 virally-infected (VI) patients (pts): 12 HIV on suppressive cART (scART; HIV-RNA<40cp/ml), 12 HCV naive to anti-HCV therapy; 30 HIV/HCV on scART and naive to anti-HCV; 8 age-matched healthy controls (HC). We measured: (i) circulating MAIT (CD3/CD8 CD161++TCRVa7.2+IL18R+) and CD161-TCRVa7.2+ frequency, activated (CD69), exhausted (PD1/ CD39), cytolytic phenotypes (granzymeB/perforin) and MAIT IL17/TNFa/IFNg following 5h E.Coli and PMA/ionomycin (flow cytometry); (ii) plasma/stool microbiome (16s) in 5 pts/group (MiSeq Illumina® tech). Statistical analyses as appropriate.

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CROI 2017