CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

530 ADAR1 SNPS INVOLVED IN SEVERITY OF LIVER DISEASE IN HIV/HCV-COINFECTED PATIENTS Luz M. Medrano 1 , Amanda Fernández-Rodríguez 1 , Juan Berenguer 2 , María Á. Jimenez-Sousa 1 , Teresa Aldámiz-Echevarría 2 , Francisco Tejerina 2 , Cristina Diez 2 , Lorena Vigón 1 , Salvador Resino 1 , for the Institute of Health Carlos III (ISCII) 1 Inst of Hlth Carlos III, Madrid, Spain, 2 Hosp Gregorio Marañon, Madrid, Spain Background: The adenosine deaminase acting on RNA (ADAR) gene is an interferon-stimulated gene involved in liver injury protection by restraining the development of liver inflammation and fibrosis. ADAR gene encodes for four similar enzymes responsible for RNA editing, which have an antiviral activity against several RNA viruses including hepatitis C virus (HCV). Other viruses such as human immune deficiency virus (HIV) uses ADAR to promote its viral life cycle. Polymorphisms at ADAR gene have been associated with sustained virological response (SVR) in chronic hepatitis B virus and HCV-infected patients. Therefore, we hypothesize that ADAR SNPs could be associated with severity of liver disease in European HIV/HCV coinfected patients. Methods: 5 SNP at ADAR gene (rs1127326, rs1127317, rs1127314, rs1127313, rs2229857) were genotyped in 220 European HIV/HCV-coinfected naive patients, by GoldenGate® assay (Illumina). Outcome variables liver disease-related were advanced fibrosis (F≥3, APRI≥1.5, and FIB-4≥3.25), severe necroinflammatory activity grade (A3) and fibrosis progression rate (FPR) higher than median (FPR≥0.075). We evaluated the genetic model that best fit our data, and multivariate regression model for analyzing the genetic association was used. Results: All SNPs were in Hardy-Weinberg equilibrium (HWE) and were associated with severity of liver disease under an additive model of inheritance. After adjusting by the most important clinical and epidemiological covariates, we detected that the presence of rs1127326 T, rs1127317 G, rs1127314 G, and rs2229857 T alleles protects against advanced liver fibrosis measured as F≥3 (adjusted odds ratios (aORs)<0.45; p<0.05), APRI≥1.5 (aORs<0.50; p<0.05) and FPR≥0.075 (aORs<0.45; p<0.05). While rs1127313 G protects against advanced fibrosis measured as F≥3 FIB4≥3.25 and FPR≥0.075 (aOR<0.44; p<0.01). These polymorphisms showed a high linkage disequilibrium (D´=1), but the values of r2 were close to 0.5 in some cases. Three major haplotypes were found (rs1127326, rs1127317, rs1127314, rs1127313 and rs2229857): CTAAC (unfavorable alleles) 51%, TGGGT (favorable alleles) 28.8%, and CTAGC 19.4%. Haplotype association analysis showed similar results to single SNP analyses. Conclusion: For the first time, we confirm that genetic variants at ADAR gene protect against severity of liver disease in HIV/HCV-coinfected patients. These findings could be used to improve therapeutic decision-making in clinical practice. 531 CB2-RR VARIANT, LINKED TO LIVER DAMAGE IN HIV/HCV CASES, MAY FAVOR HIV ACQUISITION Caterina Sagnelli 1 , Marco Merli 2 , Caterina Uberti-Foppa 2 , Giulia Bellini 1 , Hamid Hasson 2 , Nicola Coppola 1 , Adriano Lazzarin 2 , Evangelista Sagnelli 1 , Francesca Rossi 1 1 Second Univ of Naples, Naples, Italy, 2 San Raffaele Scientific Inst, Milan, Italy Background: The possibility that a rs35761398 variant of the CNR2 gene leading to the substitution of Gln (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with Arg (R) may influence the acquisition of HIV infection and the clinical course of chronic hepatitis (CH) C we compared 166 HIV/HCV coinfected with 186 HCV-monoinfected patients Methods: At enrolment, all patients, naïve for anti-HCV-treatment, underwent a percutaneous liver biopsy graded for fibrosis and necroinflammation (Ishak) by a pathologist unaware of the patients’data, and tested for CB2 rs35761398 polymorphism (TaqMan assay). Results: In HIV/HCV coinfected setting, 45.8% of patients showed the CB2-RR variant, 38.6% QR and 15.7% QQ, whereas in HCV-monoinfection CB2-RR was 31.2%r, QR 57.5% and for QQ 11.3% (p=0.005). In HIV/HCV coinfection, patients with CB2-RR showed an HAI score >9 more frequently than those with CB2-QQ or QR (65.6 vs. 24.3 and 8.1%, respectively,p<0.001), whereas in HCV-monoinfection setting this score was more frequent in CB2-QQ patients than in those CB2-QQ or QR (p=0.02). Both in HIV/HCV coinfection and HCV-monoinfection, patients with HAI >9 (37 and 43, respectively), compared with those with a lower HAI score (129 and 143, respectively) showed higher AST (p=0.000001 in both) and ALT (p=0.0004 and p=0.000001, respectively), higher fibrosis score (3.6±1.5 vs 1.9±1.4 p<0.0001 in HIV/HCV coinfection and 3.5±1.4 vs 1.9±1.2, p=0.000001 in HCV- monoinfection) and a higher steatosis score (2.0±1.3 vs 1.6±1.3, p=0.03 in HIV/HCV coinfection and 1.6±1.3 vs. 1.1±1.2 in HCV-monoinfection, p<0.03 and 0.08, respectively). Besides, patients HIV/HCV coinfection with HAI>9 more frequently than those with lower scores presented the CB2-RR variant (65.6 vs. 47.3%,p<0.01), whereas no difference and lower prevalences were observed in group B (27.9 vs. 32.2%, respectively). Finally, in ANOVA analysis of HIV/HCV coinfection and HCV-monoinfection, the patients with CB2-RR variant (p=0.003) and male sex (p=0.002) were found prevalently distributed in group A. Conclusion: The data suggest that the CB2-RR variant is associated with a more severe liver damage in CH patients with HIV/HCV coinfection and, in agreement with some recent experimental data, it might favor the acquisition of HIV infection. The data deserve further investigation. 532 PNPLA3_RS738409 VARIANT INFLUENCES PROGRESSION TO CIRRHOSIS IN HIV/HCV COINFECTION Luis M. Real 1 , Juan Macías 1 , María Mancebo 1 , Mario Frías 2 , Giovanni Dolci 3 , Francisco Téllez 4 , Dolores Merino 5 , Giovanni Guaraldi 3 , Antonio Rivero-Juárez 2 , Juan A. Pineda 1

Poster and Themed Discussion Abstracts

CROI 2017 222