CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

346 SPREAD OF HIV-DNA IN CD4+ T-CELL SUBSETS DEPENDS ON ART INITIATION TIMING Pierre Gantner 1 , Cindy Barnig 1 , Marialuisa Partisani 1 , Geneviève Beck-Wirth 2 , Jean-Pierre Faller 3 , Martin Martinot 4 , Mahsa Mohseni-Zadeh 4 , Christine Cheneau 1 , Marie-Laure Batard 1 , Patricia Fischer 1 , Béatrice Uring-Lambert 1 , Siamak Bahram 1 , David Rey 1 , Samira Fafi-Kremer 1 1 Hôpitaux Universitaires de Strasbourg, Strasbourg, France, 2 Groupe Hospital Regional–Mulhouse Sud Alsace, Mulhouse, France, 3 Hôpital Nord Franche Comté, Belfort, France, 4 Hôpital Louis Pasteur, Colmar, France Background: Life-long resting CD4+ T-cells are the major long-lasting reservoir in HIV-infected individuals. The aim of our study is to analyze the dynamics of archived HIV-DNA in CD4+ T-cells subsets in individuals starting successful dolutegravir-based regimen over 48 weeks. Methods: Participants from the prospective longitudinal DRONE study (NCT02557997) including: treatment-naïve individuals who initiated treatment with a dolutegravir-based regimen during acute (AI) or chronic (CI) infection, and treatment-experienced individuals who started a dolutegravir-based regimen while in virological success (VS) or in the aftermath of virological failure (VF), were enrolled in this substudy. Peripheral blood mononuclear cells (PBMCs) from baseline and week 48 of successful treatment were sorted in effector memory (TEM), transitional memory (TTM), central memory (TCM) and naïve (TN) CD4+ T-cells for total HIV-DNA measurements. Bayesian methods were used to estimate the posterior probability (Pr) that HIV-DNA decreased for more than 0.25 log copies/10^6 cells at week 48. Results: Twenty-seven participants (8, 5, 10, 4 individuals in the AI, CI, VS and VF group, respectively) were included. Patients were primarily male (88%) with a median age of 38 years (range, 20-54). At baseline, the highest contributions to the HIV-infected pool of CD4+ T-cells were observed in TTM cells in the AI group (62.8%), but in TCM cells for the CI, VS and VF groups (58.8%, 57.9%, 55.8%), respectively (Figure). After one year of dolutegravir-based regimen, TTM cells for the AI group (60.2%) and TCM cells for the CI, VS and VF groups (55.2%, 63.2% and 73.6%, respectively) still represented the main HIV reservoir. In these respective cells, a HIV-DNA decline was observed after 48 weeks of treatment in the AI group (4.00 to 3.26 log copies/10^6 TTM cells, Pr>99%), in the CI group (4.07 to 3.57 log copies/10^6 TCM cells, Pr=92%) and in the VF group (4.13 to 3.84 log copies/10^6 TCM cells, Pr=59%) but not in the VS group (4.19 to 4.12 log copies/10^6 TCM cells, Pr=8%). Conclusion: HIV-DNA was mainly confined to TTM or TCM cells, when antiretroviral treatment was introduced in acute or chronic HIV infection, respectively. Forty-eight weeks of a dolutegravir-based regimen lowered the HIV-DNA load in these reservoir cells when treatment was introduced in acute infection, chronic infection or in case of virological failure but not as a switching therapy.

345 MONITORING THE IMPACT OF ART MODIFICATION WITH LONGITUDINAL FDG-PET IN SIV-MODEL Sanhita Sinharay 1 , Sharat Srinivasula 2 , William T. Schreiber-Stainthorp 1 , Swati Shah 1 , Paula DeGrange 3 , Andrew Bonvillain 3 , Jing Wang 2 , Lori E. Dodd 3 , H. Clifford Lane 3 , Dima A. Hammoud 1 , Michele Di Mascio 3 1 NIH, Bethesda, MD, USA, 2 Leidos Biomedical Research, Inc, Frederick, MD, USA, 3 NIAID, Bethesda, MD, USA Background: 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. Methods: 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. Results: 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 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. correlations detected between FDG uptake and serum cytokines. Conclusion: Changes in immune activation as measured by glucose

Poster Abstracts

CROI 2018 121