CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

THURSDAY, FEBRUARY 26, 2015 Session P-C9 Poster Session

Poster Hall

2:30 pm– 4:00 pm Immune Pathogenesis of IRIS 308 Vitamin D, D-Dimer, IFNy and sCD14 Predict IRIS in a Prospective Multicenter Study LauraW. Musselwhite 1 ; AnnTierney 2 ; Susan Ellenberg 2 ; Pablo F. Belaunzarán-Zamudio 5 ; Adam Rupert 3 ; Ian Sanne 4 ; Michael M Lederman 6 ; Juan Sierra-Madero 5 ; Irini Sereti 7 1 Duke University, Durham, NC, US; 2 University of Pennsylvania, Philadelphia, PA, US; 3 Leidos Biomedical Inc., Reston, VA, US; 4 University of the Witwatersrand, Johannesburg, South Africa; 5 Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; 6 Case Western Reserve University, Cleveland, OH, US; 7 National Institutes of Health (NIH), Bethesda, MD, US Background: Immune reconstitution inflammatory syndrome (IRIS) in AIDS patients initiating anti-retroviral therapy (ART) is driven by immune dysregulation mechanisms. Biomarkers are needed to identify patients at risk. Methods: Two hundred sixty-seven ART naïve patients with CD4 <100 cells/uL were enrolled in a multicenter, randomized placebo controlled ART initiation trial in South Africa and Mexico to test whether maraviroc added to an ART regimen could prevent IRIS. Participants were followed longitudinally for 6 months and IRIS events were reviewed prospectively based on the ACTG criteria. Pre-ART cryo-preserved plasma was used to measure cytokines (IFN γ , TNF α , IL-1 β , IL-6, IL-10, IL-17), markers of myeloid cell activation (sCD14, sCD163), coagulation (D-dimer), CRP and vitamin D. Biomarkers with skewed distributions were log transformed prior to comparisons. Biomarkers in patients who developed IRIS were compared to the remaining cohort that did not develop IRIS after 6 months of follow-up. Biomarkers were then individually tested while adjusting for significant covariates selected through forward stepwise selection. Results: Participants had a median age of 36, median CD4 count of 43 cells/ m L, and median HIV-RNA 5.4 log10 copies/mL. Sixty-two participants developed IRIS and of these 21% were TB-IRIS. Patients who developed IRIS were more likely to be male (79% vs. 62%), with a prior AIDS–defining illnesses (79% vs. 54%), and a lower median hemoglobin (11.9 vs. 12.3 g/dL). Prior to ART, lower vitamin D, higher D-dimer, IFNy, and sCD14 were independently associated with risk for IRIS in a multivariate analysis. A subgroup analysis of TB-IRIS cases (N=21) vs. patients without TB-IRIS was performed and revealed baseline levels of IFN γ , CRP, and sCD14 were independent predictors of TB-IRIS risk, while vitamin D levels were not associated with TB-IRIS in univariate or multivariate analyses.

Poster Abstracts

Data represent medians with interquartile ranges. * Denotes significance after multivariate adjustment for gender, hemoglobin, and prior AIDS-defining illness. Conclusions: Biomarkers of T cell and monocyte activation (IFN γ , sCD14), coagulation (D-dimer) and low vitamin D prior to ART initiation are independently associated with IRIS. Further evaluation of these biomarkers as possible clinical prediction tools or targets of intervention for IRIS prevention is warranted. 309 LC-MS Analysis of Metabolites Differentiating IRIS FromNon-IRIS in ACTG Study A5221 Mary A. De Groote 1 ; Laura Ashton 1 ; Marisa Harton 1 ; Sam Bokatzien 2 ; KristoforWebb 1 ; Carlos Adriano Matos de Silva 1 ; Reem Al-Mubarak 1 ; Sebabratra Mahapatra 1 ; Diane Havlir 3 ; John Belisle 1 1 Colorado State University, Fort Collins, CO, US; 2 National Jewish Health, Denver, CO, US; 3 University of California San Francisco, San Francisco, CA, US Background: Immune reconstitution inflammatory syndrome (IRIS) occurs with potent treatment of HIV in the setting of co-infections such as M. tuberculosis (Mtb). IRIS is associated with substantial morbidity and mortality. We sought to better understand this syndrome and to develop a metabolic biosignature in plasma from subjects that developed IRIS. Samples were obtained from subjects enrolled in the immediate treatment arm of ACTG study A5221. Methods: Subjects from the IRIS and Non-IRIS were matched for age, gender, and CD4 cells by the ACTG Data Center. Plasma samples from as many as 3 time points per subject (entry, IRIS window and follow-up) were analyzed. Plasma was extracted in triplicate with methanol and analyzed by liquid chromatography-mass spectrometry (LC-MS). LC-MS data were analyzed with Mass Profiler Professional (MPP) software (Agilent, Inc.) and XCMS online (Scripps Institute) to select molecular features (MFs) that distinguished IRIS and non-IRIS samples based on statistical significance.

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CROI 2015