Effectiveness Of Direct-acting Antiviral Therapy Research Articles

Effectiveness of direct-acting antiviral therapy among Aboriginal and Torres Strait Islander peoples with HCV infection in Australia: A national real-world cohort (REACH-C).

Aboriginal and Torres Strait Islander peoples experience a disproportionate burden of hepatitis C virus (HCV) infection. This study assessed the effectiveness of direct-acting antiviral (DAA) therapy among Aboriginal peoples in the three years following universal access in Australia. REACH-C, a national multicentre prospective cohort study, evaluated HCV treatment outcomes from sequential DAA initiations across 33 health services between March 2016 and June 2019. DAA effectiveness was assessed by sustained virological response (SVR) in the total (full analysis set) and effectiveness (modified analysis set excluding those lost to follow-up) populations. Overall, 915 (10%) Aboriginal and 8095 (90%) non-Indigenous people commenced DAA therapy, of whom 30% and 16% reported current injecting drug use and 73% and 42% were treated in primary care, respectively. SVR in the total and effectiveness populations was 74% and 94% among Aboriginal people and 82% and 94% among non-Indigenous people, with loss to follow-up contributing to lower SVR in the total population analysis (22% Aboriginal, 13% non-Indigenous). Among Aboriginal people, returning for follow-up was positively associated with older age (aOR 1.20; 95% CI 1.04, 1.39) and SVR was negatively associated with cirrhosis (aOR 0.39; 95% CI 0.19, 0.80) and prior DAA treatment (aOR 0.14; 95% CI 0.04, 0.49). Factors reflecting higher vulnerability or inequity were not associated with returning for testing or SVR. DAA therapy was highly effective among Aboriginal peoples with HCV treated through primary and tertiary services. Tailored community-led interventions are necessary to optimize follow-up and engagement. Sustained DAA uptake and equitable access to care, treatment and prevention are required for HCV elimination.

Liver Transplantation from a Human Leukocyte Antigen-Matched Sibling Donor: Effectiveness of Direct-Acting Antiviral Therapy against Hepatitis C Virus Infection

Through living-donor liver transplantation (LDLT) from a human leukocyte antigen (HLA)-matched sibling donor, it may be possible to stop the use of immunosuppressants. It is possible that acute antibody-mediated rejection and chronic active antibody-mediated rejection through the positivity of donor-specific anti-HLA antibodies and/or T cell-mediated rejection may affect the prognosis of liver transplantation. The etiologies of liver diseases of the recipient may also affect the post-transplantation course. Herein, we report on the successful re-treatment with direct-acting antiviral (DAA) therapy against hepatitis C virus (HCV) infection in a patient who underwent a LDLT from HLA-matched sibling donor. After liver transplantation for HCV-related liver diseases, it is easy for HCV to re-infect the graft liver under a lack of immunosuppressants. DAA therapy against HCV re-infection immediately after transplantation should be commenced, and it is important to eradicate HCV for better prognosis of the recipients in LDLT for HCV-related liver diseases.

Value of Triage Treatment Strategies to Distribute Hepatitis C Direct-Acting Antiviral Agents in an Integrated Healthcare System: A Cost-Effectiveness Analysis

ObjectivesThis study aimed to assess the cost-effectiveness of fibrosis-based direct-acting antiviral treatment policies for patients with chronic hepatitis C virus at the Kaiser Permanente Mid-Atlantic States health system. MethodsWe used a Markov model to compare the lifetime costs and effects of treating patients with chronic hepatitis C virus at different stages of disease severity, or all stages simultaneously, based on a fibrosis score from the US healthcare sector perspective and societal perspective. The initial distribution of patients across fibrosis scores, the effectiveness of direct-acting antiviral therapy, and follow-up and monitoring protocols were specific to the Kaiser Permanente Mid-Atlantic States health system. Direct and indirect costs, transition probabilities, and utilities were derived from the literature. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of our results. ResultsThe “Treat All” option was dominant from both the societal and healthcare sector perspectives. The conclusion was robust in deterministic sensitivity analysis. The range of incremental costs between the less restrictive policies was small—the difference between the “Treat F1+” and the “Treat All” option was only $111 per person. Probabilistic sensitivity analyses showed, at both the $100 000/quality-adjusted life-year and $150 000/quality-adjusted life-year thresholds, there was a 70% chance that the “Treat All” option was more cost-effective than the “Treat F1+” option. ConclusionsWe found that expanded treatment access is cost-effective and, in many cases, cost saving. Although our results are primarily applicable to a regional integrated healthcare system, it offers some direction to any healthcare setting faced with resource constraints in the face of highly priced drugs.

Initial uptake, time to treatment, and real-world effectiveness of all-oral direct-acting antivirals for hepatitis C virus infection in the United States: A retrospective cohort analysis

BackgroundData on initiation and utilization of direct-acting antiviral therapies for hepatitis C virus infection in the United States are limited. This study evaluated treatment initiation, time to treatment, and real-world effectiveness of direct-acting antiviral therapy in individuals with hepatitis C virus infection treated during the first 2 years of availability of all-oral direct-acting antiviral therapies.MethodsA retrospective cohort analysis was undertaken using electronic medical records and chart review abstraction of hepatitis C virus-infected individuals aged >18 years diagnosed with chronic hepatitis C virus infection between January 1, 2014, and December 31, 2015 from the Indiana University Health database.ResultsEight hundred thirty people initiated direct-acting antiviral therapy during the 2-year observation window. The estimated incidence of treatment initiation was 8.8%±0.34% at the end of year 1 and 15.0%±0.5% at the end of year 2. Median time to initiating therapy was 300 days. Using a Cox regression analysis, positive predictors of treatment initiation included age (hazard ratio, 1.008), prior hepatitis C virus treatment (1.74), cirrhosis (2.64), and history of liver transplant (1.5). History of drug abuse (0.43), high baseline alanine aminotransferase levels (0.79), hepatitis B virus infection (0.41), and self-pay (0.39) were negatively associated with treatment initiation. In the evaluable population (n = 423), 83.9% (95% confidence interval, 80.1–87.3%) of people achieved sustained virologic response.ConclusionIn the early years of the direct-acting antiviral era, <10% of people diagnosed with chronic hepatitis C virus infection received direct-acting antiviral treatment; median time to treatment initiation was 300 days. Future analyses should evaluate time to treatment initiation among those with less advanced fibrosis.

Experience of a Portuguese Center: Effectiveness of Direct-Acting Antiviral Therapy for Hepatitis C.

In late 2014, Portugal implemented a national program for the treatment of patients with chronic hepatitis C with directactingantiviral agents. This program has made Portugal one of the first European countries to implement a structured measure oftreatment to eliminate this serious public health problem. The aim of this study was to assess the effectiveness of direct-acting antiviraltherapy in the treatment of patients with chronic hepatitis C virus infection. A retrospective observational study was conducted at Centro Hospitalar de Lisboa Ocidental on the nationalonline platform from December 2014 until February 2017 and included patients with hepatitis C virus infection who underwent treatment.The primary endpoint was sustained virologic response at least 12 weeks post treatment. Data was analyzed with the SPSS 17.0program. During the study period, 820 patients completed therapy and achieved sufficient follow-up time to assess sustained virologicresponse with an overall response rate of 97.2% (n = 797) and a response rate of 98.0%, 99.5%, 90.9%, 95.1% and 94.2% forgenotypes 1a, 1b, 2, 3 and 4, respectively. Data suggested that advanced fibrosis (F3/F4), human immunodeficiency virus co-infectionand treatment failure with interferon and ribavirin were not negatively related with sustained virologic response in our population.Most patients (80.1%) completed treatment with ledipasvir/sofosbuvir ± ribavirin. The most common adverse events were fatigue andinsomnia followed by headache and weight loss. Patients predominantly had genotype 1 infection which correlates with HCV distribution in Europe, but we found a majorproportion in genotype 4 which can be explained by immigration from African countries. Our patients' ages ranging from 22 to 90 years,reflected a new approach with no upper age limit. Direct-acting antivirals regimens resulted in remarkably high SVR rates compared tointerferon-based regimens, which were consistent with clinical trials data. Our data showed that direct-acting antiviral-based regimens are safe and have a high success rate in the treatment ofpatients with hepatitis C virus infection in a real-world setting.

Effectiveness of Direct-Acting Antiviral Therapy in Patients With Human Immunodeficiency Virus-Hepatitis C Virus Coinfection in Routine Clinical Care: A Multicenter Study.

BackgroundDirect-acting antiviral (DAA) therapy have been shown to be highly successful in clinical trials and observational studies, but less is known about treatment success in patients with a high burden of comorbid conditions, including mental health and substance use disorders. We evaluated DAA effectiveness across a broad spectrum of patients with human immunodeficiency virus (HIV)–hepatitis C virus (HCV) coinfection in routine clinical care, including those with psychosocial comorbid conditions.MethodsThe primary end point was sustained virologic response (SVR), defined as HCV RNA not detected or <25 IU/mL ≥10 weeks after treatment. We calculated SVR rates and 95% confidence intervals (CIs) in a modified intent-to-treat analysis. We repeated this analysis after multiply imputing missing SVR values.ResultsAmong 642 DAA-treated patients, 536 had SVR assessments. The median age was 55 years; 79% were men, 59% black, and 32% white. Cirrhosis (fibrosis-4 index>3.25) was present in 24%, and 17% were interferon treatment experienced; 96% had genotype 1 infection and 432 (81%) had received ledipasvir-sofosbuvir. SVR occurred in 96.5% (95% CI, 94.5%–97.9%). Patients who were black, treatment experienced, or cirrhotic all had SVR rates >95%. Patients with depression and/or anxiety, psychotic disorder, illicit drug use, or alcohol use disorder also had high SVR rates, ranging from 95.4% to 96.8%. The only factor associated with lower SVR rate was early discontinuation (77.8%; 95% CI, 52.4%–93.6%). Similar results were seen in multiply imputed data sets.ConclusionsOur study represents a large multicenter examination of DAA therapy in HIV/HCV-coinfected patients. The broad treatment success we observed across this diverse group of patients with significant comorbid conditions is highly affirming and argues for widespread implementation of DAA therapy.

Provider verification of electronic health record receipt and nonreceipt of direct-acting antivirals for the treatment of hepatitis C virus infection

PurposePharmacoepidemiologic studies using electronic health record data could serve an important role in assessing safety and effectiveness of direct-acting antiviral therapy for chronic hepatitis C virus (HCV) infection, but the validity of these data needs to be determined. We evaluated the accuracy of pharmacy fill records in the national Veterans Health Administration (VA) Corporate Data Warehouse (CDW) as compared to facility-level electronic health record. MethodsPatients prescribed a direct-acting antiviral regimen at five VA sites between 2014 and 2016 were randomly selected and reviewed. A random sample of patients with chronic HCV infection without evidence of HCV treatment during the study period also underwent chart review. We calculated positive predictive value and negative predictive value overall and by site. ResultsOf the 501 patients who received a total of 2416 prescriptions, 494 were validated using data extracted from CDW 6 months after the study period, yielding a positive predictive value of 98.6% (95% confidence interval, 97.6%–99.6%). Of the 100 patients with chronic HCV infection without prescriptions for HCV treatment, 99 were confirmed not to have received antiviral treatment (negative predictive value, 99.0%; 95% confidence interval, 97.1%–100%). ConclusionsThese findings provide assurance to researchers who use national VA CDW data for retrospective cohort studies that the CDW contains accurate information on HCV therapies in the modern treatment era.

AV1 - Cost-Effectiveness of Staged Direct-Acting Antiviral Treatment Policies in an Integrated Healthcare System

To assess the cost-effectiveness of fibrosis-based direct-acting antiviral (DAA) treatment policies for chronic Hepatitis C (HCV) patients at the Kaiser Permanente Mid-Atlantic States health system (KPMAS). We used a Markov model to compare the lifetime costs and effects of treating chronic HCV patients at different stages of disease severity based on a fibrosis score. The initial distribution of patients across fibrosis scores, the effectiveness of DAA therapy and follow-up and monitoring protocols used to build the model were specific to the KPMAS system. Other parameters, including direct and indirect costs, transition probabilities and health state utilities were derived from the literature. We performed both deterministic and probabilistic sensitivity analyses to assess the robustness of our results. The universal, or 'Treat All', treatment option was the dominant strategy from both the societal and health care sector perspectives. Varying the model parameters in a deterministic analysis did not change this conclusion. It is important to note that the range of incremental costs between the three less restrictive policies was very small – the difference between the ‘Treat F1+’ and the ‘Treat All’ option was just under $100 per person. Probabilistic sensitivity analyses showed, at both the $100,000/QALY and $150,000/QALY thresholds, there was a 70% chance that the ‘Treat All’ option was cost-effective and a 30% chance the ‘Treat F1+’ option was cost-effective. Our results are consistent with the current literature on the value of treating patients with the new DAA therapies – expanded treatment access is cost-effective and in many cases cost saving. While our results are primarily applicable to a unique integrated health care system, the results offer some direction to any health care setting that is faced with resource constraints in the face of these highly priced drugs.

Effectiveness of direct-acting antiviral therapy for hepatitis C in difficult-to-treat patients in a safety-net health system: a retrospective cohort study

BackgroundDirect-acting antivirals (DAAs) have revolutionized chronic hepatitis C (HCV) treatment, but real-world effectiveness among vulnerable populations, including uninsured patients, is lacking. This study was conducted to characterize the effectiveness of DAAs in a socioeconomically disadvantaged and underinsured patient cohort.MethodsThis retrospective observational study included all patients undergoing HCV treatment with DAA-based therapy between April 2014 and June 2016 at a large urban safety-net health system (Parkland Health and Hospital System, Dallas, TX, USA). The primary outcome was sustained virologic response (SVR), with secondary outcomes including treatment discontinuation, treatment relapse, and loss to follow-up.ResultsDAA-based therapy was initiated in 512 patients. The cohort was socioeconomically disadvantaged (56% uninsured and 13% Medicaid), with high historic rates of alcohol (41%) and substance (50%) use, and mental health disorders (38%). SVR was achieved in 90% of patients (n = 459); 26 patients (5%) were lost to follow-up. SVR was significantly lower in patients with decompensated cirrhosis (82% SVR; OR 0.37, 95% CI 0.16–0.85) but did not differ by insurance status (P = 0.98) or alcohol/substance use (P = 0.34). Reasons for treatment failure included loss to follow-up (n = 26, 5%), viral relapse (n = 16, 3%), non-treatment-related death (n = 7, 1%), and treatment discontinuation (n = 4, 1%). Of patients with viral relapse, 6 reported non-compliance and have not been retreated, 5 have been retreated and achieved SVR, 4 have undergone resistance testing but not yet initiated retreatment, and 1 was lost to follow-up.ConclusionsEffective outcomes with DAA-based therapy can be achieved in difficult-to-treat underinsured populations followed in resource-constrained safety-net health systems.

Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study.

The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome.

Cost Effectiveness of Direct-Acting Antiviral Therapy for Treatment-Naive Patients With Chronic HCV Genotype 1 Infection in the Veterans Health Administration

The Veterans Health Administration (VHA) is the largest single provider of care for hepatitis C virus (HCV) infection in the United States. We analyzed the cost effectiveness of treatment with the HCV protease inhibitors boceprevir and telaprevir in a defined managed care population of 102,851 patients with untreated chronic genotype 1 infection. We used a decision-analytic Markov model to examine 4 strategies: standard dual-therapy with pegylated interferon-alfa and ribavirin (PR), the combination of boceprevir and PR triple therapy, the combination of telaprevir and PR, or no antiviral treatment. A sensitivity analysis was performed. Sources of data included published rates of disease progression, the census bureau, and VHA pharmacy and hospitalization cost databases. The estimated costs for treating each patient were $8000 for PR, $31,300 for boceprevir and PR, and $41,700 for telaprevir and PR. Assuming VHA treatment rates of 22% and optimal rates of sustained virologic response, PR, boceprevir and PR, and telaprevir and PR would reduce relative liver-related deaths by 5.2%, 10.9%, and 11.5%, respectively. Increasing treatment rates to 50% would reduce liver-related deaths by 12%, 24.7%, and 26.1%, respectively. The incremental cost-effectiveness ratios were $29,184/quality-adjusted life-years for boceprevir and PR and $44,247/quality-adjusted life-years for telaprevir and PR vs only PR. With the current 22% treatment rate, total system-wide costs to adopt boceprevir and PR or telaprevir and PR would range from $708 to $943 million. Despite substantial up-front costs of treating HCV-infected patients in the VHA with PR, or telaprevir and PR, each regimen improves quality of life and extends life expectancy by reducing liver-related morbidity and mortality, and should be cost effective. Further efforts to expand access to direct-acting antiviral therapy are warranted.