CROI 2016 Abstract eBook

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Poster Abstracts

Results: Two HBsAg mutations (alone or in association) significantly correlate with HCC: P203Q (17.4% [4/23] in HCC vs 0.8% [1/110] in non-HCC, P=0.003), S210R (34.8% [8/23] in HCC vs 3.6% [4/110] in non-HCC, P<0.001), P203Q+S210R (17.4%[4/23] in HCC vs 0% in non-HCC). They reside in transmembrane C-terminal domain critical for HBsAg secretion. By UDPS, the intra-patient prevalence of P203Q and S210R is >50% in 100% and 71.4% of HCC-pts, indicating their selection in the viral population. Conversely, in non-HCC pts carrying P203Q and S210R, their intra-patient prevalence exceeds 50% in only 1 patient. I n vitro , the presence of P203Q, S210R and P203Q+S210R reduces the ratio of secreted/ intracellular HBsAg compared to wt at each time point (P<0.05), with the strongest decrease observed at 4 days (Ratio:4.4±0.3 for wt; 2.2±0.2 for P203Q; 3.5±0.2 for S210R; 2.3±0.2 for P203Q+S210R, P=0.05-0.005). By flow cytometry, P203Q and P203Q+S210R significantly correlate with an increased % of cells in the S phase, indicating cell cycle progression: P203Q (26±13%) and P203Q+S210R (29±14%) compared to wt (18±9%) (P<0.01). Conclusions: Key mutations, in C-terminal HBsAg domain, correlate with HBV-related HCC in vivo . They affect HBsAg release and promote cell proliferation in vitro , suggesting their potential involvement in HCC development. Their detection may help identifying patients at higher HCC-risk that may deserve intensive liver monitoring, or early anti-HBV therapy. 571 Liver Transplantation in HIV/HBV-Coinfected Patients: A Cohort Study Christian Manzardo 1 ; Fernando Aguero 2 ; Miguel Montejo 3 ; Marino Blanes 4 ; Manuel Abradelo 5 ; Santos del Campo 6 ; Lluis Castells 7 ; Antoni Rafecas 8 ; Antoni Rimola 1 ; José M. Miro 9 ; for the Spanish LiverTransplantation in HIV-Infected PatientsWorking Group. 1 Hosp Clinic-IDIBAPS-Univ of Barcelona, Barcelona, Spain; 2 Hosp Clínic de Barcelona, Barcelona, Spain; 3 Hosp Universitario Cruces, Barakaldo, Spain; 4 Hosp Universitari La Fe, Valencia, Spain; 5 Hosp Universitario 12 de Octubre, Madrid, Spain; 6 Hosp Ramon y Cajal, Madrid, Spain; 7 Hosp Universitario Vall d’Hebron, Barcelona, Spain; 8 Hosp de Bellvitge-IDIBELL, Univ of Barcelona, L’ Hospitalet de Llobregat, Spain; 9 Hosp Clinic-IDIBAPS, Univ de Barcelona, Barcelona, Spain Background: Prognosis of HIV/HBV coinfected patients undergoing liver transplantation (LT) has been reported as satisfactory. However, this contention is based on reports including small series of patients. This study aims to determine patient and graft survival rates in a larger series of patients with HIV and HBV infection who underwent LT and compare themwith those observed in HBV-infected LT recipients without HIV infection. Methods: 271 consecutive HIV-infected patients who underwent LT between 2002 and 2012 and who were followed until December 2014 were matched with 813 LT recipients without HIV infection in 22 Spanish institutions. Matched criteria were: same site, age (±12 years), gender, calendar year (±1 year), and LT indication. Those patients with HBV infection constitute the present study cohort. Results: 45 (17%) HIV/HBV-coinfected LT recipients and 135 (17%) HBV-infected patients without HIV infection were included. 37 (82%) HIV-infected and 114 (84%) HIV- uninfected patients also had HCV infection. 17 (46%) HIV/HBV/HCV-coinfected patients and 107 (95%) of HBV/HCV-coinfected patients had detectable RNA HCV at LT ( p <0.001). After a median follow-up of 5.8 (IRQ: 3.3-7.5) years, 9 (20%) HIV-infected patients and 46 (34%) HIV- uninfected patients died ( p =0.081). The main cause of death was post-LT HCV recurrence in both groups (22% each). Patient survival rates (95% CI) at 1, 3, and 5 years for HIV-infected vs. HIV-uninfected patients were 91% (78-97) vs. 91% (85-95), 87% (73-94) vs. 84% (69-92), and 84% (69-92) vs. 76% (67-82), respectively ( p =0.079) ( Figure ). 4 (9%) HIV-infected patients and 12 (9%) HIV uninfected patients underwent liver retransplantation. Graft survival rates (95% CI) at 1, 3, and 5 years for HIV-infected vs. HIV-uninfected patients were 87% (73-94) vs. 86% (79-91), 82% (68-91) vs. 73% (65-80), and 80% (64-89) vs. 70% (61-77), respectively ( p =0.065). Detectable serum HCV RNA at LT was the only factor associated with mortality in the whole series (HR 95% CI: 2.42, 1.18-4.95; p =0.015). Conclusions: HIV/HBV-infected patients undergoing LT have a patient and graft survival not different than those in HBV-infected patients without HIV infection. HCV coinfection with detectable HCV RNA at LT is associated with a worse outcome.

Poster Abstracts

572 Incidence and Risk Factors of Acute Rejection in HIV+ Liver Transplant Recipients Christian Manzardo 1 ; Fernando Aguero 2 ; Antoni Rafecas 3 ; Jesús Fortún 4 ; Marino Blanes 5 ; Magdalena Salcedo 6 ; Itxarone Bilbao 7 ; Asunción Moreno 1 ; Antoni Rimola 1 ; José M. Miro 8 ; for the Spanish Foundation for AIDS Research and Prevention, LiverTransplantation Investigators 1 Hosp Clinic-IDIBAPS-Univ of Barcelona, Barcelona, Spain; 2 Hosp Clínic de Barcelona, Barcelona, Spain; 3 Hosp de Bellvitge-IDIBELL, Univ of Barcelona, L’ Hospitalet de Llobregat, Spain; 4 Hosp Ramon y Cajal, Madrid, Spain; 5 Hosp Universitari La Fe, Valencia, Spain; 6 Hosp General Universitario Gregorio Marañón, Madrid, Spain; 7 Hosp Universitario Vall d’Hebron, Barcelona, Spain; 8 Hosp Clinic-IDIBAPS, Univ de Barcelona, Barcelona, Spain Background: HIV-infected liver transplant (LT) recipients seem to have higher rates of acute rejection than recipients without HIV infection. We determined the incidence and risk factors of acute rejection in HIV-infected LT recipients in comparison with HIV-uninfected LT recipients Methods: 271 consecutive HIV infected patients who underwent LT between 2002-2012 were matched with 813 patients without HIV infection (1:3 ratio) who underwent LT during the same period in 22 Spanish institutions. Other matched criteria were age (± 12 years), gender, calendar year (± 1 year), and LT indication. All acute rejections were biopsy-proven. Results: After a median follow-up of 4.4 (IQR: 2.1-7.0) years, 85 (36%) HIV-infected and 151 (19%) HIV-uninfected patients developed acute rejection ( p <0.001). Cumulative incidence of acute rejection (95% CI) at 1, 3, and 5 years in LT recipients with and without HIV infection was 32% (26-38) vs. 16% (14- 19), 33% (27-39) vs. 19% (16-22), and 33%

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