CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

763 NOVEL BIOMARKERS PREDICTIVE OF NON-AIDS EVENTS DURING ART- MEDIATED VIRAL SUPPRESSION Martin Hoenigl 1 , Carlee Moser 2 , Nicholas Funderburg 3 , Ronald Bosch 2 , Amy Kantor 2 , Yonglong Zhang 4 , Jesper Eugen-Olsen 5 , Malcolm Finkelman 4 , Alan Landay 6 , Michael M. Lederman 7 , Sara Gianella 8 1 University of California San Diego, San Diego, CA, USA, 2 Harvard University, Cambridge, MA, USA, 3 The Ohio State University, Columbus, OH, USA, 4 Associates of Cape Cod, Inc, Falmouth, MA, USA, 5 Hvidovre Hospital, Hvidovre, Denmark, 6 Rush University Medical Center, Chicago, IL, USA, 7 Case Western Reserve University, Cleveland, OH, USA, 8 University of California San Diego, La Jolla, CA, USA Background: Antiretroviral therapy (ART) treated HIV infection is associated with increased risk of morbidity/mortality, driven in part by increased inflammation. Potential contributors to inflammation include translocation of bacterial and fungal products from the gut into systemic circulation and pro-inflammatory lipids, but direct linkages between these indices and clinical events have not been adequately demonstrated. Here, in a case/control study, we measured levels of plasma biomarkers that have been associated previously with microbial translocation (i.e. lipopolysaccharide binding protein [LBP], beta-D-glucan [BDG], intestinal fatty acid binding protein [I-FABP]), oxidized [ox]LDL), and chronic inflammation and monocyte activation (soluble urokinase plasminogen activator receptor [suPAR], soluble CD163 [sCD163]), to identify potential associations among biomarker levels and non-AIDS events (myocardial infarction, stroke, cancer, serious bacterial infection and non-accidental death). Methods: Participants (143 cases, 315 controls) were selected from the ACTG ALLRT trial; all were virally suppressed on ART at year 1, and thereafter (Tenorio, PMID:24795473). Plasma samples were selected: pre-ART initiation, 1-year post-ART, and immediately preceding an event (cases). Controls had an event- free follow-up equal or greater than that of the relevant case, and participants were matched on age (median 45 years), sex (85%male), pre-ART CD4+ count (median 215 cells/mm 3 ), ART regimen, and parent study. LBP, BDG, I-FABP, sCD163, and oxLDL were measured at all timepoints; suPAR was measured in baseline samples only. At each timepoint, conditional logistic regression analysis assessed associations of the biomarkers with events, and adjusted for relevant covariates. Results: At baseline, higher levels of suPAR were associated with increased risk of non-AIDS events in both unadjusted and adjusted analyses (Table 1). At year 1 post-ART and pre-event, higher levels of BDG and LBP were associated with increased risk of non-AIDS events in unadjusted and adjusted analyses. Associations were not observed for I-FABP, sCD163 and oxLDL. Conclusion: Elevated levels of suPAR pre-ART were associated with development of non-AIDS events post-ART. After 1 year of ART, elevated BDG and LBP were predictive of non-AIDS events, similar to IL-6, D-dimer, and sTNFR-I and –II (Tenorio, PMID: 24795473). These biomarkers may inform future interventional studies aimed at reducing morbidity and mortality in ART-treated HIV infection.

764 INFLAMMATION AND IMMUNE ACTIVATION MARKERS ASSOCIATED WITH NON-AIDS CANCERS IN HIV Muhaimen Siddiqui 1 , Elizabeth Breen 2 , Jay Bream 1 , Yue Chen 3 , Dana H. Gabuzda 4 , Eric C. Seaberg 1 1 Johns Hopkins University, Baltimore, MD, USA, 2 University of California Los Angeles, Los Angeles, CA, USA, 3 University of Pittsburgh, Pittsburgh, PA, USA, 4 Dana–Farber Cancer Institute, Boston, MA, USA Background: The incidence of non-AIDS defining cancers (NADCs) is elevated among PLWH, and this difference may be promoted by persistent inflammation and immune activation during HIV infection. The objective of this study was to examine the association of inflammation and immune activation with incident NADCs among HIV+men enrolled in the Multicenter AIDS Cohort Study (MACS). Methods: Matched case-control study among MACS participants with 23 serummarkers of inflammation and immune activation and C-reactive protein (CRP) tested in longitudinal samples obtained between 1984 and 2009. Cases included 66 HIV-infected men diagnosed with a NADC during follow-up who had serummarkers measured 0-2 years before NADC diagnosis. Controls included cancer-free men who were individually matched (1:1) to cases on age, race, smoking history, BMI, CD4 T-cell count, HIV RNA level, duration of effective ART, and calendar year. We examined the association of the serum markers with incident NADCs both overall and separately for NADCs with and without a known viral etiology (i.e., HPV, HBV, HCV, and EBV). Marker levels were log 2 -transformed, and the adjusted percent difference (PD) in the mean levels between cases and controls was estimated using GEEs to account for matching. The Benjamini-Hochberg method was used to determine statistical significance (α=0.05) controlling for a false discovery rate of 25%. Results: The mean age of cases was 52, 71%were Caucasian, 24%were eART naive, mean CD4 was 489, and 17% had CD4<200; controls were similar on all matching factors. CXCL13 (PD:23%), IFN-γ (PD:53%), IL-10 (PD:70%), IL-6 (PD:47%), BAFF (PD:27%), and CRP (PD:56%) were significantly elevated among NADC cases compared to controls. For NADCs with a known viral etiology, the same markers plus CXCL10 (PD:64%) and sIR-2Rα (PD:41%) were significantly (p<0.05) elevated among cases. In contrast, no significant differences were observed for NADCs without a known viral etiology (see figure). Conclusion: Several inflammation and immune activation markers were elevated prior the diagnosis of incident NADC among men living with HIV. However, statistically significant elevation of these markers was observed only for NADCs with a known viral etiology. It remains to be determined whether the association between elevated serummarkers and development of NADCs is due to HIV-related immune dysregulation, products of developing tumors or tumor microenvironment, or immune responses to coinfection with oncogenic viruses.

Poster Abstracts

CROI 2018 286