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High sustained virological response rates using imported generic direct acting antiviral treatment for hepatitis C.

ABSTRACT: High prices of direct acting antivirals (DAAs) for hepatitis C virus (HCV) can lead to restrictions on access to treatment in high- and middle-income countries. An increasing number of people in these countries are treating their HCV infection with generic drugs produced in India, China, Bangladesh or Egypt. This analysis assessed the efficacy of generic imported DAAs.Patients sourced generic versions of sofosbuvir (SOF), ledipasvir (LDV) and daclatasvir (DCV) from suppliers in India, Bangladesh, China and Egypt via three buyers' clubs. The choice of DAAs and the length of treatment were determined on baseline RNA levels, HCV genotype and stage of fibrosis. Patient HCV RNA levels were evaluated pre-treatment, during treatment, at end of treatment (EOT) and then for sustained virological response (SVR) at 4, 12, and 24 weeks, normally by a treating clinician.Overall 616 patients submitted results: 199 from an Australian buyers' club, 205 from a South-east Asian buyers' clubs, and 212 from an Eastern European buyers' club. Of the 616 patients treated, 276 received SOF/LDV (35 with ribavirin [RBV]) and 340 received SOF/DCV (61 with RBV). At baseline, 61% were male, 52% had HCV genotype 1 and 11% had liver cirrhosis. The mean age was 44.3 years and the mean baseline HCV RNA was 6.9 log10 IU/mL. A rapid virological response (RVR) was observed in 314/375 (84%) of the patients treated. Based on currently available data, the percentage of patients with HCV RNA below the lower limit of quantification (LLoQ) was 99% (234/237) at EOT, 99% (299/303) at SVR4 and 99% (247/250) at SVR12.In this analysis, treatment with imported generic DAAs achieved high rates of HCV RNA undetectability at the end of treatment, and SVR12 in 99% of patients evaluated to date. Mass treatment with generic DAAs is a feasible and economical alternative route of accessing curative DAAs, where the high prices for branded alternatives prevent access to treatment.

SUBMITTER: Hill A

PROVIDER: S-EPMC5632545 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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High sustained virological response rates using imported generic direct acting antiviral treatment for hepatitis C.

Hill Andrew A Khwairakpam Giten G Wang James J Golovin Sergey S Dragunova Julia J Smith Rachel R Houghton-Price Vicky V Korologou-Linden Roxanna R Nath Sanjay S Savage Anna A Jefferys Greg G

Journal of virus eradication 20171001 4

<h4>Background</h4>High prices of direct acting antivirals (DAAs) for hepatitis C virus (HCV) can lead to restrictions on access to treatment in high- and middle-income countries. An increasing number of people in these countries are treating their HCV infection with generic drugs produced in India, China, Bangladesh or Egypt. This analysis assessed the efficacy of generic imported DAAs.<h4>Methods</h4>Patients sourced generic versions of sofosbuvir (SOF), ledipasvir (LDV) and daclatasvir (DCV) ...[more]

PMID: 29057082

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Project description:ImportanceSome payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection.ObjectiveTo evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR).Design, setting, and participantsThis retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023.ExposureAlcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD.Main outcomes and measuresThe primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category.ResultsAmong 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11 215 (16.2%) had high-risk consumption or AUD. After adjustment for potential confounding variables, there was no difference in SVR across alcohol use categories, even for patients with high-risk consumption or AUD (OR, 0.95; 95% CI, 0.85-1.07). There was no evidence of interaction by stage of hepatic fibrosis measured by fibrosis-4 score (P for interaction = .30).Conclusions and relevanceIn this cohort study, alcohol use and AUD were not associated with lower odds of SVR. Restricting access to DAA therapy according to alcohol use creates an unnecessary barrier to patients and challenges HCV elimination goals.

Project description:IntroductionRandomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment with direct-acting antiviral (DAA) treatment in individuals with HIV and HCV co-infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non-random samples of individuals with available post-DAA HCV-RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co-infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV-RNA testing.MethodsWe included adults with HIV-HCV co-infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV-RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g-formula to impute SVR status for individuals with no SVR assessment.Results and discussionA total of 4527 individuals who initiated DAA treatment (88% males, median [IQR] age 56 [50, 62] years) were included. Of the total of 642 (14%) individuals had no HCV-RNA test on or after 12 weeks after the end of treatment. The overall observed and g-formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post-DAA and strategies for more systematic routine HCV-RNA testing should be considered.ConclusionsOur estimates with and without adjustment for missing HCV-RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials.

Project description:IntroductionThe genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct-acting antivirals (DAA) or interferon (IFN) are still not fully understood.MethodsSixty-nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole-exome sequencing.ResultsAmong the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV-positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV-SVR. According to the HCV treatment, 35 HCV-SVR HCCs were classified into two groups: eight tumors with DAA (HCV-SVR-DAA) and 24 tumors with interferon (HCV-SVR-IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV-SVR than in HCV-positive tumors (p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV-SVR samples than in HCV-positive samples (p = 0.048). Among the patients with HCV-SVR, the frequency of samples with TP53 mutations was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors (p = 0.030). TP53 inactivation scores in HCV-SVR-DAA tumors were found to be significantly enhanced in comparison to HCV-SVR-IFN tumors (p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV-SVR-DAA tumors. HCV-SVR-DAA was significantly associated with portal vein invasion (p = 0.003) in comparison to HCV-SVR-IFN.ConclusionOur dataset potentially serves as a fundamental resource for the genomic characteristics of HCV-SVR-DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV-positive tumors and HCV-SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors.

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High sustained virological response rates using imported generic direct acting antiviral treatment for hepatitis C.

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High sustained virological response rates using imported generic direct acting antiviral treatment for hepatitis C.

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