CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

analysis of a subgroup of non-enrollers was performed for clinical and serological characteristics and factors associated with hepatitis B e antigen (HBeAg)-positivity was assessed by logistic regression. Results: Of the 353 subjects prescreened, 139 enrolled in the cohort and biopsies were obtained in 119. Enrolled patients were predominately male (92%), black (50%), HBeAg+ (62%) and had a mean age 49 (28-70) years. On biopsy 24% had evidence of Ishak 3-6 fibrosis. Clinically, some had detectable HBV DNA (20%) and HIV RNA (25%). Mean CD4 was 558 cells/μL (38-1520), ALT 36 IU (8-223) and AST 35 IU (13-202). Of all patients prescreened, 211 did not enroll in the study. The reasons for non-enrollment into the cohort study included: refusing liver biopsy (31%), hepatic decompensation (4%), hepatocellular cancer (2%), failure to consent (63%). Data was collected on 127 HBsAg+ non-enrollers who were predominately male (84%), black (36%), and on cART (99%). Half were HBeAg+ (51/103), 22% (21/87) had evidence of cirrhosis of which 24% (5/21) had hepatic decompensation and 1 had liver cancer without cirrhosis, 36% had detectable HIV RNA. Mean CD4 was 478 cells/μL (3-1428), ALT 38 IU (8-284), and AST 42 IU (15-229). HBeAg+ was not associated with gender, race, or liver function tests or cirrhosis but was significantly associated with HBV DNA detectability and age (see Table). Conclusion: One fourth of HIV/HBV patients in this real world cohort had evidence of advanced liver disease. Of those in which HBeAg status was available, half were HBeAg+, which was independently associated with detectable HBV DNA and age. Focused efforts to reduce HIV and HBV viral load in younger HIV/HBV infected patients is needed to improve HBV outcomes in this group.

171 patients (28%) developed the CCO over time of whom 55/115 (48%) HDV positive, 98/403 (24%) HDV negative and 18/99 (18%) HDV unknown (p<.001, Figure).In unadjusted Cox regression analysis, RH was 2.34 95%CI:1.68-3.26; the association was attenuated after controlling for HCV coinfection (RH=1.46; 95%CI:0.98, 2.17). Other factors independently associated with higher risk of CCO were: male gender, older age, lower CD4 count, alcohol use and smoking. In the subset of people who received anti-HBV therapy, 43/79 (54%) HDV+ patients and 84/320 (26%) HDV-neg patients developed CCO (OR=3.36; 95%CI:1.95-5.78). Conclusion: Presence of anti-HDV antibodies in HIV-coinfected individuals is a marker of faster progression to severe liver disease and death even in participants who received anti-HBV therapy.

Poster Abstracts

623 GAIN OF POSITIVE CHARGES IN HBSAG C-TERMINUS CORRELATES WITH HBV-INDUCED LIVER CANCER Romina Salpini 1 , Luca Carioti 1 , Marianna Aragri 1 , Domenico Di Carlo 1 , Luna Colagrossi 1 , Giuseppina Cappiello 2 , Pascale Trimoulet 3 , Herve J. Fleury 3 , Simona Francioso 1 , Loredana Sarmati 1 , Massimo Andreoni 1 , Mario Angelico 1 , Francesca Ceccherini Silberstein 1 , Carlo F. Perno 1 , Valentina Svicher 1 1 University of Rome Tor Vergata, Rome, Italy, 2 Sandro Pertini Hospital, Rome, Italy, 3 Pellegrin Hospital, Bordeaux, France Background: Gain of positively charged amino acids (aa) can alter the folding of a transmembrane protein domain. HBsAg C-terminus is a hydrophobic transmembrane domain, composed by alpha-helices, crucial for HBsAg secretion. HBsAg misfolding in endoplasmic reticulum (ER) membrane can impair HBsAg secretion and in turn favor HBV-induced hepatocellular carcinoma (HCC). The role of mutations associated with gain of charged aa in HBsAg C-terminus on HBV-induced HCC onset is unknown. Methods: We analyze 807 HBV chronically infected patients from routine clinical practice: 28 with HCC (78.6% D; 21.4% A), and 779 patients without HCC (79.8% D; 20.2% A). Mutations associated with gain of charged aa in HBsAg C-terminus (aa189-226) are evaluated. Multivariable logistic regression model is used to assess association of mutations with HCC. The stability of a domain in a membrane is predicted by estimating hydrophobicity profiles of HBsAg C-terminus (Black,1991). I-Tasser is used to assess three-dimensional HBsAg structures (aa:1-226) and their stability (∆∆G[wt-mutated]<0 indicating decreased stability in presence of mutation based on Quan,2016). Results: The acquisition of ≥1 positively charged aa at HBsAg C-terminus positions 204, 207, and 210 strongly correlates with HCC (71.4%with HCC vs 30.2%without HCC, P<0.001). Multivariable analysis confirms this association stratifying for patients’demographics, HBV genotype, serum HBV-DNA and anti-HBV drugs use (OR[95%CI]:6.3[2.6-15.3], P<0.001). The acquisition of positively charged aa results from S204R, S207R and S210R mutations, found in 14.3%, 28.6% and 28.6% of HCC-patients, respectively. S204R, S207R and S210R decrease the hydrophobicity index of HBsAg C-terminus respect to wt (S204R:16.0, S207R:16.0, S210R:16.2 vs wt:16.4), and ∆∆G values (∆∆G[S204R- wt]=-0.27; ∆∆G[S207R-wt]=-0.11; ∆∆G[S210R-wt]=-0.14). Furthermore, a shortening of membrane-spanning alpha-helix motif is observed in presence of S204R, S207R and S210R (predicted alpha-helix length: aa209-224 for S204R,

622 HEPATITIS DELTA INFECTION IN PATIENTS WITH HIV/HBV COINFECTION Giovanni B. Gaeta 1 , Milensu Shanyinde 2 , Giuseppina Brancaccio 1 , Massimo Puoti 3 , Antonella D’Arminio Monforte 4 , Andrea De Luca 5 , Alessandra Vergori 6 , Stefano Rusconi 4 , Antonio Mazzarelli 6 , Antonella Castagna 7 , Andrea Antinori 6 , Alessandro Cozzi-Lepri 2 1 University of Campania Luigi Vanvitelli, Naples, Italy, 2 University College London, London, UK, 3 ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, 4 University of Milan, Milan, Italy, 5 Siena University Hospital, Siena, Italy, 6 Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, 7 San Raffaele Vita-Salute University, Milan, Italy Background: Hepatitis Delta virus (HDV) co-infects about 20 million HBsAg+ individuals worldwide. HIV infected persons with HBV coinfection are at risk for HDV. We explored the prevalence of HDV infection and its clinical impact in the ICONA cohort. Methods: Anti-HDV status was assessed among HBsAg+patients enrolled in1997-2015.We performed a cross-sectional analysis to compare baseline (the date of first HBV test) characteristics of HBV+/HDV+ vs. HBV+/HDV-patients. The proportion of patients HDV+ amongst patients who were HBV+ per year of enrolment was also calculated. Composite clinical outcome (CCO) was defined as the occurrence of any of the following events: Fib4 score >3.25; clinical diagnosis of cirrhosis; decompensation;hepato-carcinoma (HCC) or death. Kaplan Meier method was used to plot the time to develop the CCO,stratified by anti-HDV status. Univariable and multivariable Cox regression models adjusted for age, gender, nationality, region, education, CD4 count, HIV-RNA viral load, smoking status,alcohol consumption , mode of HIV transmission and HCV infection status, were fitted and relative hazards (RH) shown. Results: Among 13,558 HIV positive patients enrolled as of September 2015, 10,988 were HBsAg-negative, 1,953 were nottested for HBsAg and 617 patients were HBsAg-positive; of these, 115 (18.6%) wereanti-HDVpositive, 403 (65.3%) anti-HDV negative and 99 (16.0%) not tested for HDV. Proportions of anti-HDV positive cases tended to decrease from the year 1997 to 2011 (from 28% to 4%) then appear to increase to 8% in the period 2012-2015. Overall,

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