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      Treatment Outcomes of Treatment-Naïve Hepatitis C Patients Co-Infected with HIV: A Systematic Review and Meta-Analysis of Observational Cohorts

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          Abstract

          Introduction

          Co-infection with Hepatitis C (HCV) and HIV is common and HIV accelerates hepatic disease progression due to HCV. However, access to HCV treatment is limited and success rates are generally poor.

          Methods

          We conducted a systematic review and meta-analysis to assess HCV treatment outcomes in observational cohorts. Two databases (Medline and EMBASE) were searched using a compound search strategy for cohort studies reporting HCV treatment outcomes (as determined by a sustained virological response, SVR) in HIV-positive patients initiating HCV treatment for the first time.

          Results

          40 studies were included for review, providing outcomes on 5339 patients from 17 countries. The pooled proportion of patients achieving SVR was 38%. Significantly poorer outcomes were observed for patients infected with HCV genotypes 1 or 4 (pooled SVR 24.5%), compared to genotypes 2 or 3 (pooled SVR 59.8%). The pooled proportion of patients who discontinued treatment due to drug toxicities (reported by 33 studies) was low, at 4.3% (3.3–5.3%). Defaulting from treatment, reported by 33 studies, was also low (5.1%, 3.5–6.6%), as was on-treatment mortality (35 studies, 0.1% (0–0.2%)).

          Conclusions

          These results, reported under programmatic conditions, are comparable to those reported in randomised clinical trials, and show that although HCV treatment outcomes are generally poor in HIV co-infected patients, those infected with HCV genotypes 2 or 3 have outcomes comparable to HIV-negative patients.

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          Most cited references45

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          Relationship of liver disease stage and antiviral therapy with liver-related events and death in adults coinfected with HIV/HCV.

          Human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV) disease progression; however, the effect of liver disease stage and antiviral therapy on the risk of clinical outcomes is incompletely understood. To determine the incidence of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death according to baseline hepatic fibrosis and antiviral treatment for HIV/HCV coinfected individuals. Prospective cohort of 638 coinfected adults (80% black, 66% men) receiving care at the Johns Hopkins HIV clinic and receiving a liver biopsy and who were prospectively monitored for clinical events between July 1993 and August 2011 (median follow-up, 5.82 years; interquartile range, 3.42-8.85 years). Histological specimens were scored for hepatic fibrosis stage according to the METAVIR scoring system. Incidence of composite outcome of ESLD, HCC, or death. Patients experienced a graded increased risk in incidence of clinical outcomes based on baseline hepatic fibrosis stage (classification range, F0-F4): F0, 23.63 (95% CI, 16.80-33.24); F1, 36.33 (95% CI, 28.03-47.10); F2, 53.40 (95% CI, 33.65-84.76); F3, 56.14 (95% CI, 31.09-101.38); and F4, 79.43 (95% CI, 55.86-112.95) per 1000 person-years (P < .001). In multivariable negative binomial regression, fibrosis stages F2 through F4 and antiretroviral therapy were independently associated with composite ESLD, HCC, or all-cause mortality after adjustment for demographic characteristics, injection drug use, and CD4 cell count. Compared with F0, the incidence rate ratio (RR) for F2 was 2.31 (95% CI, 1.23-4.34; P = .009); F3, 3.18 (95% CI, 1.47-6.88; P = .003); and F4, 3.57 (95% CI, 2.06-6.19; P < .001). Human immunodeficiency virus treatment was associated with fewer clinical events (incidence RR, 0.27; 95% CI, 0.19-0.38; P < .001). For the 226 patients who underwent HCV treatment, the incidence of clinical events did not significantly differ between treatment nonresponders and untreated patients (incidence RR, 1.27; 95% CI, 0.86-1.86; P = .23). In contrast, no events were observed in the 51 patients with sustained virologic response (n = 36) and relapse (n = 15), including 19 with significant fibrosis. In this cohort of patients with HIV/HCV coinfection, hepatic fibrosis stage was independently associated with a composite outcome of ESLD, HCC, or death.
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            Limited effectiveness of antiviral treatment for hepatitis C in an urban HIV clinic.

            To evaluate predictors and trends of referral for hepatitis C virus (HCV) care, clinic attendance and treatment in an urban HIV clinic. A retrospective cohort analysis in which 845 of 1318 co-infected adults who attended the Johns Hopkins HIV clinic between 1998 and 2003 after an on-site viral hepatitis clinic was opened, attended regularly (>/= 1 visit/year for >/= 2 years). Logistic regression was used to examine predictors of referral. A total of 277 (33%) of 845 were referred for HCV care. Independent predictors of referral included percentage elevated alanine aminotransferase levels [adjusted odds ratio (AOR) for 10% increase,1.16; 95% confidence interval (CI), 1.10-1.22] and CD4 cell count > 350 cells/microl (AOR, 3.20; 95% CI, 2.10-4.90), while injection drug use was a barrier to referral (AOR, 0.26; 95% CI, 0.11-0.64). Overall referral rate increased from 200 cells/microl were not referred. One hundred and eighty-five (67%) of 277 referred kept their appointment, of whom 32% failed to complete a pre-treatment evaluation. Of the remaining 125, only 69 (55%) were medically eligible for treatment, and 29 (42%) underwent HCV treatment. Ninety percent of 29 were infected with genotype 1 and 70% were African American; six (21%) achieved sustained virologic response (SVR). Only 0.7% of the full cohort achieved SVR. Although the potential for SVR and the recent marked increase in access to HCV care are encouraging, overall effectiveness of anti-HCV treatment in this urban, chiefly African American, HCV genotype 1 HIV clinic is extremely low. New therapies and treatment strategies are an urgent medical need.
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              Chronic hepatitis C treatment outcomes in low- and middle-income countries: a systematic review and meta-analysis

              OBJECTIVE: To assess the effectiveness of treatment for hepatitis C virus (HCV) infection in low- and middle-income countries and identify factors associated with successful outcomes. METHODS: We performed a systematic review and meta-analysis of studies of HCV treatment programmes in low- and middle-income countries. The primary outcome was a sustained virological response (SVR). Factors associated with treatment outcomes were identified by random-effects meta-regression analysis. FINDINGS: The analysis involved data on 12 213 patients included in 93 studies from 17 countries. The overall SVR rate was 52% (95% confidence interval, CI: 48-56). For studies in which patients were predominantly infected with genotype 1 or 4 HCV, the pooled SVR rate was 49% (95% CI: 43-55). This was significantly lower than the rate of 59% (95% CI: 54-64) found in studies in which patients were predominantly infected with other genotypes (P = 0.012). Factors associated with successful outcomes included treatment with pegylated interferon and ribavirin, infection with an HCV genotype other than genotype 1 or 4 and the absence of liver damage or human immunodeficiency virus infection at baseline. No significant difference in the SVR rate was observed between weight-adjusted and fixed-dose ribavirin treatment. Overall, 17% (95% CI: 13-23) of adverse events resulted in treatment interruption or dose modification, but only 4% (95% CI: 3-5) resulted in treatment discontinuation. CONCLUSION: The outcomes of treatment for HCV infection in low- and middle-income countries were similar to those reported in high-income countries.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                5 February 2013
                : 8
                : 2
                : e55373
                Affiliations
                [1 ]Department of Infectious Diseases, Faculty of Medicine, Imperial College, London, United Kingdom
                [2 ]Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia
                [3 ]Division of Infection and Immunity, University College Hospital, London, United Kingdom
                [4 ]Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College, London, United Kingdom
                [5 ]Manson Unit, Médecins Sans Frontières, London, United Kingdom
                [6 ]Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
                [7 ]Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa
                University of North Carolina School of Medicine, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the study: AD GC NF. Performed the review: AD KPS ZS NF. Conceived and designed the experiments: AD GC NF. Performed the experiments: AD KPS ZS NF. Analyzed the data: AD ZS NF. Wrote the paper: AD KPS ZS PdC EJM GC NF.

                Article
                PONE-D-12-27515
                10.1371/journal.pone.0055373
                3564801
                23393570
                63899ca6-0442-433e-a21f-3ab025b8a1de
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 September 2012
                : 22 December 2012
                Page count
                Pages: 10
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Computer Science
                Information Technology
                Databases
                Medicine
                Clinical Research Design
                Systematic Reviews
                Drugs and Devices
                Gastroenterology and Hepatology
                Liver Diseases
                Infectious Hepatitis
                Hepatitis C
                Infectious Diseases
                Viral Diseases
                Hepatitis
                HIV

                Uncategorized
                Uncategorized

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