CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

619 PROGRESSIVE HBSAG LOSS IN HIV-HBV COINFECTED INDIVIDUALS ON TDF-INCLUSIVE cART Jennifer Audsley 1 , Anchalee Avihingsanon 2 , Margaret Littlejohn 1 , Scott Bowden 1 , Gail Matthews 3 , Christopher K. Fairley 4 , Sharon R. Lewin 1 , Joseph Sasadeusz 1 1 Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia, 2 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 3 Kirby Institute, Sydney, NSW, Australia, 4 Alfred Hospital, Melbourne, VIC, Australia Background: Tenofovir disoproxil fumarate (TDF) is effective in suppressing HIV and HBV replication in HIV-HBV co-infection, although HBV DNA can persist in some individuals on TDF-containing combination antiretroviral therapy (ART). HBV resistance to TDF has not been reported to date. We initiated this study to assess long-term HBV suppression and the frequency of HBsAg seroconversion on TDF Methods: We enrolled 92 HIV-HBV co-infected participants on or about to commence TDF-containing ART from Australia (n=41) and Thailand (n=52) in a prospective longitudinal study, with access to pre-TDF samples and data for those who commenced TDF prior to study entry. Participants were followed every 6 months for 2 years and then annually to 5 years, with clinical and laboratory assessments including HBV DNA, HBs and HBe serology, CD4 count and HIV RNA. This study compares follow-up at 2 years (Yr2) and 5 years (Yr5) Results: Data were available for 92.4% (n=85) and 78.3 % (n=72) of the cohort at Yr2 and Yr5, respectively. The median [IQR] duration on TDF was 6.8 years (5.9-10.0) at Yr 5. 91.8% had undetectable HBV DNA (<20 IU/ML) at Yr 2 and this increased to 98.5% by Yr5. The one individual with detectable HBV DNA at Yr5 had a viral load too low (31 IU/ml) for sequencing, detectable HIV RNA (33,957 copies/ml), reported adherence to ART but had no mutations associated with HIV-related ARV resistance. By Yr 2 and 5, 7 and 11 participants respectively had lost HBsAg – 12.0% of the cohort by Yr5. Acquisition of HBsAb was also observed in two of these participants at Yr2, and a further two participants by Yr5. Two further participants gained sAb but did not lose sAg. Median (range) duration on TDF to HBsAg loss was 48 months (29-88) (survival curve - Figure 1). HBe serology changes at Yr5 were observed in 9 participants, including HBeAg loss/seroconversion (n=2), gain of HBeAg (n=4) and loss or gain of HBeAb (n=3). There were 3 deaths in the cohort, 2 from liver disease (hepatoma and end-stage liver disease) and 1 suicide. ALT, AST, ALP, GGT and LDH were all significantly lower at Yr 5 compared Yr 2 (Wilcoxon signed rank test) Conclusion: Detectable HBV DNA after 5 years of follow-up was rare in HIV-HBV co-infected participants on TDF-containing ART. HBV serological changes continued over time and liver biochemistry improved, however liver-related deaths were still observed. Further follow up will be needed to determine if improvement continues with very long-term duration on TDF.

620 DETERMINANTS OF LIVER COMPLICATIONS AMONG HIV/HEPATITIS B-COINFECTED PATIENTS Vincent Lo Re 1 , Craig W. Newcomb 1 , Dena M. Carbonari 1 , Jason A. Roy 1 , Mari Kitahata 2 , Joseph Lim 3 , Michael J. Silverberg 4 , Angel Mayor 5 , Michael A. Horberg 6 , Edward R. Cachay 7 , Mark Hull 8 , Richard D. Moore 9 , Marina Klein 10 , H. Nina Kim 2 1 University of Pennsylvania, Philadelphia, PA, USA, 2 University of Washington, Seattle, WA, USA, 3 Yale University, New Haven, CT, USA, 4 Kaiser Permanente Northern California, Oakland, CA, USA, 5 Universidad Central del Caribe, Bayamon, Puerto Rico, 6 Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA, 7 University of California San Diego, San Diego, CA, USA, 8 University of British Columbia, Vancouver, BC, Canada, 9 Johns Hopkins University, Baltimore, MD, USA, 10 McGill University, Montreal, QC, Canada Background: Chronic hepatitis B (HBV) remains a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) among HIV/HBV patients. Yet, the factors contributing to these liver complications in this group have not been thoroughly examined. Methods: We evaluated the determinants of liver complications in HIV and HBV (positive HBV surface antigen, e antigen, or HBV DNA) coinfected patients in 9 US and Canadian clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal bleed, hepatic encephalopathy) and HCC diagnoses from 1996-2010. Our outcome was a composite of first occurrence of ESLD or HCC diagnosis. Multivariable Cox regression was used to examine hazard ratios (HRs) and 95% confidence intervals of hypothesized factors associated with ESLD/HCC, including age ≥40 years, male sex, non-black/non-Hispanic race, diabetes, HIV RNA and CD4 count (as time-updated variables), history of at-risk alcohol use, hepatitis C coinfection, and baseline liver fibrosis by FIB-4. We also performed Cox regression to determine if increasing consecutive time with suppressed HIV RNA (≤500 copies/mL) on antiretroviral therapy (ART) was associated with lower rates of ESLD/HCC. Results: Among 3,123 HIV/HBV patients (85%male; 38% non-black/non- Hispanic; 83% prescribed ART; 53% prescribed tenofovir-based ART) followed for 11,343 person-years, 185 incident ESLD/HCC events occurred (incidence rate=16.3 [14.0-18.8] events/1,000 person-years). Non-black/non-Hispanic race (HR=1.91 [1.34-2.73]), higher baseline FIB-4 (>3.25: HR=2.63 [1.72-4.03]; 1.45-3.25: HR=1.46 [1.01-2.10]), and lower CD4 count (<200 cells/μL: HR=4.09 [2.49-6.71]; 201-499 cells/μL: HR=1.96 [1.22-3.17]) were associated with increased rates of ESLD/HCC. HRs were similar when the cohort was restricted to the 1,643 patients on tenofovir-based ART. Increasing consecutive time with suppressed HIV RNA on ART was associated with a lower risk of ESLD/HCC (<6 months: HR=0.87 [0.54-1.40]; 6-12 months: HR=0.66 [0.36-1.22]; >12 months: HR=0.53 [0.35-0.81]; test for trend p=0.002). Conclusion: Non-black/non-Hispanic race, higher baseline FIB-4, and lower time-updated CD4 count were risk factors for ESLD/HCC among HIV/HBV patients. Patients with >12 months of viral suppression were significantly less likely to develop ESLD/HCC. Clinicians should ensure that HIV/HBV patients maintain HIV suppression on ART to reduce their risk of liver complications. 621 HIGH PREVALENCE OF ADVANCED LIVER DISEASE AMONG AN HIV/HBV REAL-WORLD COHORT Mamta K. Jain 1 , Mandana Khalili 2 , Raymond T. Chung 3 , Kranthi Vysyaraju 1 , David Wong 4 , Mauricio Lisker-Melman 5 , Mark Sulkowski 6 , Marc Ghany 7 , Richard K. Sterling 8 1 University of Texas Southwestern, Dallas, TX, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 Massachusetts General Hospital, Boston, MA, USA, 4 Toronto General Hospital, Toronto, ON, Canada, 5 Washington University in St Louis, St Louis, MO, USA, 6 Johns Hopkins Hospital, Baltimore, MD, USA, 7 NIH, Bethesda, MD, USA, 8 Virginia Commonwealth University, Richmond, VA, USA Background: The HIV/HBV Cohort is a prospective ancillary study of the Hepatitis B Research Network (HBRN) whose goal is to define the clinical, virological, serological and histological characteristics of a cohort of HBV/HIV patients in North America on combination antiretroviral therapy (cART). We report on the HIV/HBV prescreened participants who did not enroll in the study. Methods: We enrolled HIV/HBV patients from 8 centers across North America, obtained liver biopsies, and examined clinical, virological and serological characteristics. Those who were prescreened but did not enroll in the study were examined as a representation of a “real world cohort”. Reasons for not participating in the ancillary study were obtained. A retrospective descriptive

Poster Abstracts

CROI 2018 229