CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

568 Alcohol Use, Hepatitis B, and Liver Fibrosis Among HIV-Infected Persons inWest Africa

Antoine Jaquet 1 ; GillesWandeler 2 ; Marcellin Nouaman 3 ; Didier Ekouevi 4 ; JudicaëlTine 5 ; Ahuatchi P. Coffie 3 ; AristophaneTanon 6 ; Moussa Seydi 5 ; Alain Attia 7 ; Francois Dabis 1 1 INSERM U897, ISPED, Univ de Bordeaux, Bordeaux, France; 2 Univ Hosp Bern, Bern, Switzerland; 3 Prog PACCI, CHU Treichville, Abidjan, Côte d’Ivoire; 4 INSERM U897, ISPED, Univ de Bordeaux, Abidjan, Côte d’Ivoire; 5 CHU de Fann, Dakar, Senegal; 6 CHU de Treichville, Abidjan, Côte d’Ivoire; 7 CHU de Yopougon, Abidjan, Côte d’Ivoire Background: Liver diseases represent a leading cause of mortality in people living with HIV (PLWHIV) in industrialized countries. Little is known about liver fibrosis and the associated factors among PLWIHV in sub-Saharan Africa. Methods: A liver fibrosis screening programwas undertaken in three HIV referral clinics in Côte d’Ivoire, Senegal and Togo, West Africa. PLWIHIV attending their usual clinic appointment and who agreed to the study were consecutively enrolled and underwent a non-invasive assessment of liver fibrosis using both liver stiffness measure (LSM) with transient elastography and the aspartate aminotransferase to platelet ratio index (APRI). Significant liver fibrosis (≥F2 METAVIR score) was defined as an LSM≥7.1 kPa among patients with an APRI score ≥0.5. The short alcohol use disorder identification test (AUDIT-c) was administered to identify hazardous alcohol use (AUDIT-c ≥4) and heavy alcohol use (AUDIT-c ≥6) based on a 12-point score. All patients were tested for Hepatitis B virus (HBV) surface antigen (HBsAg) using a rapid test (Determine®) and if positive, followed by viral load quantification. A multivariate logistic regression model was used to identify factors associated with liver fibrosis using Odds Ratio (OR) with 95% Confidence Interval (CI). Results: A total of 807 PLWHIV (69.8%women) were included at a median age of 43 years [interquartile range (IQR): 36-50]. Their median CD4 count was 393 cells/mm 3 [IQR 234 – 563] and 682 (84.5%) were on antiretroviral therapy (ART). A significant liver fibrosis was reported in 5.3% (95% CI 3.8–6.7) of participants. At the time of the survey, 76 (9.5%) patients reported hazardous alcohol use and 32 (4.0%) heavy alcohol use. Of 74 (9.2%) HBsAg-positive patients, 63 (85.1%) were on ART and among them 37 (58.7%) were on a tenofovir (TDF)-based regimen. Among the 26 HBsAg-positive patients with a detectable HBV viral load, those exposed to TDF and/or lamivudine had lower rates of detectable HBV viral load (29.0%) compared to unexposed patients (66.6%) (p=0.01). In multivariate analyses, heavy alcohol use [OR=4.5 (95% CI 1.8–11.1)], [Ref. AUDIT-c<4] and HBV infection [OR= 2.6 (95% CI 1.1-6.5)] were associated with significant liver fibrosis. Conclusions: Heavy alcohol use was identified as an important determinant of liver fibrosis among PLWHIV in West Africa. Screening of alcohol use and specific interventions to prevent alcohol abuse should be proposed to PLWHIV, along with the recent WHO recommendations to screen for HBV infection. 569 Baseline IL-18 Level Is AssociatedWith HBeAg Seroconversion in HIV/HBV Coinfection Yijia Li 1 ; Jing Xie 1 ;Yang Han 1 ; HuanlingWang 1 ; NidanWang 1 ;Ting Zhu 1 ; Xiaojing Song 1 ;Yanling Li 1 ; ChloeThio 2 ;Taisheng Li 1 1 Peking Union Med Coll Hosp, Beijing, China; 2 Johns Hopkins Univ, Baltimore, MD, USA Background: In HIV/HBV co-infected patients, hepatitis B e antigen (HBeAg) seroconversion is associated with lower rates of developing cirrhosis and hepatocellular carcinoma. A previous animal study suggests that interleukin-18 (IL-18), a cytokine associated with interferon-γ production and anti-viral defense, inhibits HBV replication. Recent studies also find that IL-18 polymorphisms are associated with immune control of HBV in HBV mono-infected patients. However, whether IL-18 is associated with HBeAg seroconversion in HIV/ HBV co-infected patients is unknown. Methods: We enrolled 35 treatment-naïve, HBeAg positive, HIV/HBV co-infected patients. HBV DNA, HIV RNA, CD4 cell count, HBV surface antigen (HBsAg) quantification (qHBsAg), HBeAg quantification (qHBeAg) and IL-18 levels were measured prior to, at 24 and 48 weeks of HBV-active antiretroviral therapy (ART). Primary endpoint was HBeAg seroconversion. Multivariate Poisson regression models with robust standard errors were used to determine factors associated with HBeAg seroconversion. Results: Twenty-one patients received tenofovir (TDF)+ lamivudine (3TC) based ART while 14 patients received 3TC-based ART. Median baseline HBV DNA levels were 8.04 log IU/ml (upper limit of detection). After 48 weeks of treatment, 10 patients experienced HBeAg seroconversion. In comparison with non-seroconverters, seroconverters had higher median HIV RNA (5.22 vs. 4.58 log copies/ml, P=0.030), lower median qHBsAg (3.97 vs. 4.76 log IU/ml, P=0.011), lower median qHBeAg (1.61 vs. 3.01 log PEIU/ml, P=0.004), and marginally higher median IL-18 (511.1 vs. 335.9 pg/ml, P=0.068) prior to ART. In the multivariate regression model, IL-18 levels (RR 5.13 per 1 log pg/ml increase, P=0.004), CD4 cell count (RR 1.92 per 100 cells/μl increase, P=0.011), HIV RNA (RR 2.01 per 1 log copy/ml increase, P=0.001) and qHBsAg (RR 0.17 per 1 log IU/ml increase, P=0.012) were significantly associated with HBeAg seroconversion. Conclusions: In HIV/HBV co-infected patients with HBeAg positivity, high IL-18 levels, CD4 cell count, HIV RNA load, as well as low qHBsAg prior to ART were associated with HBeAg seroconversion.

Poster Abstracts

570 HBsAg Mutations CorrelateWith HCC, Affect HBsAg Release, and Favor Cell Proliferation Valentina Svicher 1 ; Romina Salpini 1 ; Matteo Surdo 1 ; NadiaWarner 2 ; Michela Pollicita 1 ; Francesca Ceccherini-Silberstein 1 ; Massimo Andreoni 3 ; Mario Angelico 3 ; Stephen Locarnini 2 ; Carlo Federico Perno 4 1 Univ of Rome Tor Vergata, Rome, Italy; 2 Victorian Infectious Diseases Reference Lab, Victoria, Australia; 3 Tor Vergata Univ, Rome, Italy; 4 Univ of Rome Tor Vergata, Roma, Italy Background: To evaluate HBsAg genetic elements associated with HBV-induced liver cancer (HCC) and their impact on cell proliferation. Methods: This study includes 133 HBV chronically infected patients (pts): 23 with HCC (73.9% HBV genotype D; 26.1% A), and 110 asymptomatic pts as control (72.7% D, 27.3% A). HBsAg mutations (detected in plasma samples) are defined according to the reference sequence of each specific genotype. Association of mutations with HCC is assessed by Fisher test. HBsAg ultra-deep sequencing (UDPS) is performed for 13 HCC- and in 24 non-HCC pts.HBsAg mutations are introduced into a 1.3x genome-length HBV genotype D. WT and mutated clones are transfected into Huh7 cells. Lysates and supernatants are harvested in triplicate daily until day 5 post-transfection, and HBsAg quantified by Alexxis assay. Mutations are also introduced into a pIRES II plasmid encoding HBsAg and GFP. Cell cycle is analysed by flow cytometry (DNA propidium iodide-staining) on transfected GFP+ cells at day 7 post transfection (4 experiments in triplicate).

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CROI 2016