Started Hepatitis C Virus Treatment Research Articles

Ribavirin and abacavir drug interaction in HIV–HCV coinfected patients

To examine the impact of ribavirin and abacavir coadministration on hepatitis C virus (HCV) virological response and trough ribavirin plasma concentration (Cmin) in HIV-HCV coinfected patients. Pharmacokinetic substudy on patients from the ANRS CO-13 HEPAVIH cohort. Patients receiving ribavirin-pegylated interferon for whom a ribavirin steady state Cmin was prospectively determined were included. Rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) as well as HCV-RNA decline were evaluated. Overall, 124 HIV-HCV coinfected patients (95% on antiretroviral therapy) were enrolled. Of these patients, 22% received abacavir. The overall median (interquartile range) ribavirin Cmin was 1.6 mg/l (1.2-2.2) with no statistical difference between abacavir users and nonusers [1.5 mg/l (0.99-2.1) and 1.7 (1.2-2.3), P = 0.15]. RVR and EVR were 52 and 72%, respectively. There was no difference observed in the proportion of abacavir users vs. nonusers achieving RVR (respectively 59 vs. 50%, P = 0.40) or EVR (72 vs. 73%, P = 0.94), or in the HCV-RNA decline at week 4 [-2.24 log(10) IU/ml, (-3.58; -0.81) and -1.27 (-2.8; -0.47) P = 0.28] or at week 12 [-1.76 log(10) IU/ml (-3.67; -0.35) and -1.85 (-3.13; -1.13) (P = 0.58)]. The SVR rate was 45% for abacavir users and 24% for abacavir nonusers, but the difference was not statistically significant (P = 0.059). In our study, there was no evidence that abacavir affected HCV treatment outcomes and the ribavirin Cmin was similar in abacavir users and nonusers, confirming the absence of pharmacokinetic interaction between abacavir and ribavirin. An abacavir-containing regimen is, therefore, a well tolerated treatment alternative for coinfected patients starting HCV treatment.

Telaprevir-Based Triple Therapy of Hepatitis C Infection in a Patient with Hemophilia A and Factor VIII Inhibitor: Decreased Need for Factor VIII with Viral Suppression

Purpose: Chronic hepatitis C virus (HCV) infection has been a heavy burden to patients with hemophilia. Patients with hemophilia A frequently receive transfusion of factor VIII as part of their management which can lead to development of antibodies that can neutralize factor VIII. HCV infection by itself and its treatment with interferon can lead to the development of autoantibodies including acquired factor VIII inhibitor. Therefore, treating HCV in hemophiliacs with factor VIII inhibitor remains challenging. A 22-year-old male with a history significant for hereditary hemophilia A complicated by refractory high titer factor VIII inhibitors and hepatitis C genotype 1a infection diagnosed at the age of 1 year was referred to our clinic regarding hepatitis C treatment. The patient has been treated with recombinant human factor VIII 6,000 IU Bid to maintain his factor level at around 20%. He was also receiving rituximab (to help decrease his factor VIII autoantibodies) every 4-6 months for 3 years. Liver biopsy was not performed prior to starting HCV treatment due to concerns about bleeding and the patient was HCV treatment naive. Patient was started on hepatitis C telaprevir-based triple therapy (telaprevir 750 mg TID, weight based ribavirin, and peg-interferon α-2a) with good virologic response (HCV RNA was undetectable at treatment weeks 4, 12, and 24). He qualified for response-guided therapy and he completed his treatment at 24 weeks. He tolerated therapy relatively well without the need to dose reduce his ribavirin or peg-interferon α-2a. Interestingly, within a few days after starting telaprevir therapy, his factor VIII level started to increase significantly and after four weeks of hepatitis C treatment, his factor VIII inhibitor screen was negative and his need for recombinant factor VIII decreased by 50% as shown in the Figure. To our knowledge, this is the first case report on using telaprevir-based triple therapy in a hemophilia patient with factor VIII inhibitor. This case demonstrates that HCV therapy was safe and that suppressing HCV may help decrease factor VIII inhibitor level and the need for recombinant factor VIII. We hope that our report will encourage other practicing clinicians to treat this challenging patient population.Figure: [1069]Disclosure: Naim Alkhouri, MD - Speaker's Bureau and Advisory Board Member of Vertex (makers of telaprevir). Nizar N Zein: - Speaker's Bureau and Advisory Board Member of Vertex (makers of telaprevir).

Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the prescribing physician and patients' beliefs (ANRS CO13 HEPAVIH cohort, France)

BackgroundTreatment for the hepatitis C virus (HCV) may be delayed significantly in HIV/HCV co-infected patients. Our study aims at identifying the correlates of access to HCV treatment in this population.MethodsWe used 3-year follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled patients living with HIV and HCV. We included pegylated interferon and ribavirin-naive patients (N = 600) at enrolment. Clinical/biological data were retrieved from medical records. Self-administered questionnaires were used for both physicians and their patients to collect data about experience and behaviors, respectively.ResultsMedian [IQR] follow-up was 12[12-24] months and 124 patients (20.7%) had started HCV treatment. After multiple adjustment including patients' negative beliefs about HCV treatment, those followed up by a general practitioner working in a hospital setting were more likely to receive HCV treatment (OR[95%CI]: 1.71 [1.06-2.75]). Patients followed by general practitioners also reported significantly higher levels of alcohol use, severe depressive symptoms and poor social conditions than those followed up by other physicians.ConclusionsHospital-general practitioner networks can play a crucial role in engaging patients who are the most vulnerable and in reducing existing inequities in access to HCV care. Further operational research is needed to assess to what extent these models can be implemented in other settings and for patients who bear the burden of multiple co-morbidities.

Antiviral Drugs and the Treatment of Hepatitis C

With effective treatment of HIV-1, hepatitis C virus (HCV) has become increasingly recognized as a major cause of morbidity and mortality in this population. Rapid progression of liver disease and cirrhosis has been documented in HIV/HCV co-infected individuals, particularly with lower CD4-counts (< 200/μL). Therefore, HCV treatment has become a priority for many clinicians, despite the presence of many. An important issue among HIV/HCV co-infected patients is the selection of antiretroviral therapy (ART) during treatment with pegylated interferon, ribavirin (RBV), plus new HCV protease inhibitors. Extensive drug-drug interactions (DDI) and overlapping drug-associated adverse events can impact the outcome of HCV therapy. In this review, we focus on the important data and studies regarding optimizing antiretroviral regimens before starting HCV treatment in HIV/HCV co-infected patients to increase the chance of sustained virologic response (SVR).

Positive impact of hepatitis C virus (HCV) treatment on antiretroviral treatment adherence in human immunodeficiency virus–HCV coinfected patients: one more argument for expanded access to HCV treatment for injecting drug users

Treatment for the hepatitis C virus (HCV) may be delayed significantly in human immunodeficiency virus (HIV)/HCV coinfected patients on antiretroviral treatment (ART) for fear that its burden could compromise ART adherence. However, the effect such treatment has on ART adherence in observational settings remains largely unknown. Longitudinal data were used to investigate the relationship between initiating HCV treatment and adherence to ART in HIV/HCV coinfected patients. The French national prospective cohort of patients coinfected with HIV and HCV (ANRS-CO-13-HEPAVIH) is a multi-centre cohort. Seventeen out-patient hospital services delivering HIV and HCV care in France. HIV/HCV coinfected patients on ART (n = 593 patients, 976 visits). Self-administered questionnaires and medical records. A mixed logistic regression model based on generalized estimates equations (GEE) to identify factors associated with non-adherence to ART. Among the 593 patients, 36% were classified as non-adherent to ART at the enrolment visit and 12% started HCV treatment during follow-up. ART adherence was not associated statistically with HCV treatment initiation. The proportion of patients maintaining adherence or becoming adherent to ART for those starting HCV treatment was higher than in the rest of the sample (P = 0.07). After multiple adjustment for known correlates, such as poor housing conditions, binge drinking, recent drug use and depressive symptoms, patients who initiated HCV treatment were less likely to be non-adherent to ART [odds ratio (95% confidence interval) = 0.41 (0.24-0.71)]. Engaging human immunodeficiency virus/hepatitis C virus coinfected individuals in hepatitis C virus treatment is associated with high adherence to antiretroviral treatment. Physicians should prioritize hepatitis C virus treatment as part of a multi-disciplinary approach.

A Sustained Virologic Response Reduces Risk of All-Cause Mortality in Patients With Hepatitis C

The effectiveness of hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin usually is evaluated by the surrogate end point of sustained virologic response (SVR), although the ultimate goal of antiviral treatment is to reduce mortality. The impact of SVR on all-cause mortality is not well documented by HCV genotype or in populations in routine medical practice with substantial comorbidities. From the US Department of Veterans Affairs (VA), we identified all patients infected with HCV genotypes 1, 2, or 3, without human immunodeficiency virus co-infection or hepatocellular carcinoma before HCV treatment with pegylated interferon and ribavirin, who started HCV treatment from January 2001 to June 2007, stopped treatment by June 2008, and had a posttreatment HCV RNA test result of SVR or no SVR. Mortality data from VA and non-VA sources were available through 2009. HCV genotypes 1, 2, or 3 cohorts consisted of 12,166, 2904, and 1794 patients, respectively, with SVR rates of 35%, 72%, and 62%, respectively. Each cohort had high rates of comorbidities. During a median follow-up period of approximately 3.8 years, 1119 genotype-1, 220 genotype-2, and 196 genotype-3 patients died. In genotype-specific multivariate survival models that controlled for demographic factors, comorbidities, laboratory characteristics, and treatment characteristics, an SVR was associated with substantially reduced mortality risk for each genotype (genotype-1 hazard ratio, 0.70; P < .0001; genotype-2 hazard ratio, 0.64; P = .006; genotype-3 hazard ratio, 0.51; P = .0002). An SVR reduced mortality among patients infected with HCV of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial comorbidities.

Sexually transmitted reinfection with a new hepatitis C genotype during pegylated interferon and ribavirin therapy

Hepatitis C (HCV) is an important cause of liver disease worldwide, and intravenous drug use (IVDU) is the most important risk factor in the western world. A minority of cases is sexually transmitted. Double or reinfections with a different HCV genotype are rare. Reinfection with different HCV strains has been reported in multitransfused thalassaemic children [1] and recently in one intravenous drug user during interferon treatment [2]. Reinfection during the most effective HCV treatment [3] has never been described. We report a case of a 30-year-old homosexual man who developed an acute HCV infection with a new strain during pegylated-interferon (PEG-IFN) and ribavirin treatment for his first acute HCV infection. In 2002, an asymptomatic homosexual HIV-1-positive patient with a CD4 cell count of 670 × 106 cells/l was referred to our outpatient clinic. From 1998 to 2004 he was treated for several sexually transmitted diseases (gonorrhoea, syphilis, rectal lymphogranuloma venereum). Blood examination showed normal liver enzymes and no HCV antibodies or HCV RNA. As the CD4 cell count decreased to 270 × 106 cells/l, treatment with zidovudin/lamivudine/nevirapine was started, with a good virological response. In October 2003 (Fig. 1, t = 5 months) an increase of aspartate aminotransferase (AST) was thought to be nevirapine related, and this drug was substituted by lopinavir/ritonavir. As the AST levels only decreased slightly, he mentioned participation in sex parties, during which he had unprotected receptive anal intercourse with many penises and fists (‘fist-fucking’), and one of the participants was HCV positive. HCV antibodies of the patient showed seroconversion between January and May 2003, with a HCV-RNA load up to 1.92 × 109 copies/ml of genotype 1. Treatment with PEG-IFN-α2a, 180 μg/week and ribavirin 1000 mg/day was started, and lamivudine/tenofovir/lopinavir/ritonavir was continued. HCV RNA was cleared after 12 weeks and AST levels normalized (Fig. 1). At month 13, still on PEG-IFN/ribavirin therapy, AST levels increased and HCV RNA became detectable. Genotyping by Inno-LIPA HCV reverse hybridisation assay (InnoGenetics, Belgium) showed genotype 2. The patient admitted he had participated in one more ‘fist-fucking’ party at month 11 in Berlin. The patient denied IVDU at any time.Fig. 1: Patient's data in time. Serum aspartate aminotransferase (AST) levels (▪), and CD4 cell counts (•), are plotted on the left Y axis, HIV RNA (▾), and hepatitis C virus (HCV) RNA (▴) are plotted on the right Y axis. The treatment time of highly active antiretroviral therapy (zidovudine/lamivudine/nevirapine) and the switch to lamivudine/tenofovir/lopinavir/ritonavir and the treatment period of pegylated interferon (PEG-IFN-α2a)/ribavirin are indicated with the time bars below the figure. LPV, Lopinavir; NVP, nevirapine; RBV, ribavirin; RTV, ritonavir; TDF, tenofovir; 3TC, lamivudine; ZDV, zidovudine. For the quantitative and qualitative HCV-RNA assay the lower limit of detection was 1000 resp. 200 copies/ml. Samples detectable with the qualitative assay, but less than 1000 copies/ml were plotted as 500 copies/ml.This is the first reported case of reinfection with HCV during intensive treatment with PEG-IFN and ribavirin, which suggests a failure of the prevention of HCV. This case questions the prophylactic use (before any sign of infection) of PEG-IFN after accidental HCV exposure. Furthermore, starting HCV treatment in patients who continue risky behaviour (IVDU and homosexual promiscuous behaviour such as fisting), is therefore questionable.