CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

594 High Prevalence of Anti-HEV IgG Is Not AssociatedWith HIV Infection in Rakai, Uganda Denali Boon 1 ; Andrew D. Redd 2 ; Oliver Laeyendecker 3 ; Ponsiano Ocama 4 ; Steven J. Reynolds 3 ; Ronald H. Gray 5 ; Robert H. Purcell 2 ;Thomas C. Quinn 6 ; Lara Stabinski 7 ; for the Rakai Health Sciences Program 1 Johns Hopkins Univ, Baltimore, MD, USA; 2 NIAID, NIH, Bethesda, MD, USA; 3 NIH, Bethesda, MD, USA; 4 Makerere Univ Coll of Hlth Scis, Kampala, Uganda; 5 Johns Hopkins Bloomberg Sch of PH, Baltimore, MD, USA; 6 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA; 7 Office of the US Global AIDS Coordinator, US Dept of State, Washington, DC, USA Background: Hepatitis E virus (HEV) infections are generally acute self-limiting infections, however, in select populations such as pregnant women, it can cause severe disease with a high mortality. There is limited information on the prevalence of HEV in sub-Saharan Africa, particularly in the context of HIV-infection and liver disease. We evaluated correlates of prior exposure to HEV in a rural Ugandan population with a high burden of HIV associated liver fibrosis. Methods: The study population was comprised of 985 subjects from the Rakai Community Cohort Study, sampled between 2008-2009, with a mean age of 37.9 (range 18.5 to 83.0), 33%were male, and 50% HIV+. All participants were tested for HEV Immunoglobulin G (IgG) serology performed on serum or plasma using an in-house sandwich based enzyme immunoassay (EIA). All samples testing positive for anti-HEV IgG as well as all anti-HEV IgG negative samples with a CD4 cell count ≤ 200 cells/μL were tested for anti-HEV Immunoglobulin M (IgM) using an in-house class capture EIA. All samples positive for anti-HEV IgM along with a random subset of samples with a high titer of IgG anti-HEV, or CD4 count < 200 cells/μl were tested for HEV RNA. Hepatitis B surface antigen (HBsAg), Schistosomiasis, and HIV-1 were determined using standard assays. Liver stiffness was determined using transient elastography. Prevalence risk ratios (PRR) with robust variance were estimated using modified Poisson regression to assess correlates of anti-HEV IgG seropositivity. Results: The seroprevalence for anti-HEV IgG was 47%. Male gender (PRR=1.265; 95% CI: 1.088, 1.470; p=0.002) and chronic HBV infection (PRR=1.395; 95% CI: 1.109, 1.756; p=0.005) were associated with an increased prevalence of anti-HEV IgG (Table 1). HIV status (PRR=0.973; 95% CI: 0.852, 1.111; p=0.683) was not associated with anti-HEV IgG. Genotype 3 HEV RNA was detected in serum from a single individual who worked in agriculture and was HIV infected. Conclusions: These data suggest a large burden of exposure to HEV among HIV-infected and HIV-uninfected individuals in rural Uganda. Prior exposure to HEV was associated with male gender and chronic HBV infection. There was little evidence of active or chronic HEV infection.

Poster Abstracts

595 Oxylipin Metabolites As Markers of Inflammation and Liver Disease in HCV Infection Susanna Naggie 1 ; Eric G. Meissner 2 ; Lisa St. Johns-Williams 3 ;WillThompson 3 ; Derek Cyr 3 ; Joseph Lucas 3 ; Arthur Moseley 3 ; Shyam Kottilil 4 ; Keyur Patel 5 1 Duke Univ Sch of Med, Durham, NC, USA; 2 Med Univ of South Carolina, Charleston, SC, USA; 3 Duke Univ, Durham, NC, USA; 4 Univ of Maryland Med Cntr, Baltimore, MD, USA; 5 Duke Clinical Rsr Inst, Durham, NC, USA Background: Chronic hepatitis C virus (HCV) infection is associated with metabolic effects including dyslipidemia and insulin resistance (IR), which contributes to disease progression and affects response to therapy. We have previously shown that sofosbuvir (SOF)/ribavirin (RBV) mediated clearance of HCV results in changes in lipid metabolic pathways implicating a direct effect of HCV replication on lipid homeostasis. Oxylipins are bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids and contribute to inflammatory responses associated with IR and cardiovascular disease. In this study, we investigated changes in oxylipins associated with the stage of liver disease and treatment outcomes in chronic HCV patients. Methods: Twenty HCV GT1 subjects (n=10 SVR, n=10 relapse) treated with SOF/RBV for 24 weeks (SPARE HCV trial), were selected for this analysis. A targeted plasma oxylipin analysis (N=111 metabolites, high performance liquid chromatography-tandemmass spectrometry) was conducted on plasma samples at baseline and weeks 4 and 20 on therapy. Clinical data (outcome and histology) were available from the SPARE trial. Paired and unpaired t-tests were used to compare between groups. Results: Our cohort was predominantly male (70%), mean age 52 years, and 80% black. There were no differences in baseline characteristics between SVR and relapsers. Several oxylipin metabolites differed by study outcome result (SVR vs relapse), and fibrosis stage (Table). Pooling all timepoints, subjects with relapse had higher oxylipin levels, whether pro- or anti-inflammatory, suggesting greater immune dysregulation. Treatment related clearance (SVR) resulted in a decrease in the pro-/anti-inflammatory ratio of key oxylipin metabolites (5-HETE/(11,12-DiHETrE+14,15-DiHETrE) (p=0.034). Conclusions: For the first time, we demonstrate differential expression of pro- and anti-inflammatory lipid metabolites in HCV-infected subjects treated with SOF/RBV, which differ by treatment response and fibrosis stage. Furthermore, clearance of HCV appears to result in improved immune dysregulation. In a clinical cohort of HIV/HCV patients we have identified oxylipin metabolites are associated with stage of liver disease and correlated these metabolites with serummarkers of chronic inflammation. These preliminary data further support the role of HCV in modulation of host lipid homeostasis and identifies intermediary lipidomic pathways leading to the chronic inflammation seen with chronic hepatitis C infection.

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CROI 2016