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Successful sofosbuvir-based therapy in HIV/hepatitis C virus coinfected liver transplant recipients with recurrent hepatitis C virus infection.

ABSTRACT: Recurrent hepatitis C virus (HCV) infection contributes to unfavourable outcomes in HIV/HCV coinfected liver transplant recipients. Direct-acting antiviral (DAA) therapies for HCV offer an opportunity to improve patient and allograft survival in this patient population. We evaluated treatment outcomes with sofosbuvir (SOF)-based DAA therapy among HIV/HCV coinfected liver transplant recipients.Single centre prospective cohort study.We identified eight HIV/HCV coinfected liver transplant recipients who were prospectively followed in the Northwestern University Viral Hepatitis Registry and who received SOF-based DAA therapy. We evaluated responses to therapy, including sustained HCV viral response 12 weeks after therapy completion (SVR12) and adverse effects.Seven recipients (87.5%) completed 12 weeks of SOF-based therapy: SOF/simeprevir for genotype 1 (n?=?6), SOF/ribavirin for genotype 2 (n?=?1). Of persons who completed therapy, all achieved SVR12. Strategies for the management of expected and observed drug interactions consequent to the addition of simeprevir to preexisting complex medication regimens included modifications of HIV antiretroviral regimens (n?=?4) and tacrolimus dosing (n?=?4) and frequent monitoring of tacrolimus trough levels. Minor adverse effects were observed after DAA initiation. One episode of allograft rejection and one death occurred that were deemed unlikely related to HCV therapy.High rates of HCV treatment success and no treatment-limiting adverse effects were observed in this HIV/HCV liver transplant cohort. Complex drug interactions were successfully managed in the context of multidisciplinary specialty care. Further studies are needed to assess the long-term effects of DAA therapy on patient and allograft survival among HIV/HCV coinfected liver transplant recipients.

SUBMITTER: Grant JL

PROVIDER: S-EPMC4754111 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Successful sofosbuvir-based therapy in HIV/hepatitis C virus coinfected liver transplant recipients with recurrent hepatitis C virus infection.

Grant Jennifer L JL Hawkins Claudia C Brooks Hannah H Palella Frank J FJ Koppe Sean W P SW Abecassis Michael M MM Stosor Valentina V

AIDS (London, England) 20160101 1

<h4>Objective</h4>Recurrent hepatitis C virus (HCV) infection contributes to unfavourable outcomes in HIV/HCV coinfected liver transplant recipients. Direct-acting antiviral (DAA) therapies for HCV offer an opportunity to improve patient and allograft survival in this patient population. We evaluated treatment outcomes with sofosbuvir (SOF)-based DAA therapy among HIV/HCV coinfected liver transplant recipients.<h4>Design</h4>Single centre prospective cohort study.<h4>Methods</h4>We identified ei ...[more]

PMID: 26731756

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Project description:BACKGROUND:Hepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver complications among HIV/HBV-coinfected individuals remain unknown. SETTING:North American AIDS Cohort Collaboration on Research and Design. METHODS:We performed a retrospective cohort study among HIV/HBV-coinfected patients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios [aHRs with 95% confidence interval (CIs)] of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (?500 copies/mL). RESULTS:Among 3573 HIV/HBV patients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 [95% CI: 6.6 to 9.7] events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race [aHR = 1.76 (1.13-2.74)], diabetes mellitus [aHR = 2.07 (1.20-3.57)], lower time-updated CD4 cell count [<200 cells/mm: aHR = 2.59 (1.36-4.91); 201-499 cells/mm: aHR = 1.75 (1.01-3.06) versus ?500 cells/mm], heavy alcohol use [aHR = 1.58 (1.04-2.39)], and higher FIB-4 at start of follow-up [>3.25: aHR = 9.79 (5.73-16.74); 1.45-3.25: aHR = 3.20 (1.87-5.47) versus FIB-4 <1.45]. HIV suppression for ?6 months was associated with lower liver complication rates compared with those with unsuppressed HIV [aHR = 0.56 (0.35-0.91)]. CONCLUSIONS:Non-black/non-Hispanic race, diabetes, lower CD4 cell count, heavy alcohol use, and advanced liver fibrosis were determinants of liver complications among HIV/HBV patients. Sustained HIV suppression should be a focus for HIV/HBV-coinfected patients to reduce the risks of ESLD/HCC.

Dataset Information

Successful sofosbuvir-based therapy in HIV/hepatitis C virus coinfected liver transplant recipients with recurrent hepatitis C virus infection.

Publications

Successful sofosbuvir-based therapy in HIV/hepatitis C virus coinfected liver transplant recipients with recurrent hepatitis C virus infection.

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