Hepatitis C Virus Medications Research Articles

Impact of pill burden on adherence to hepatitis C medication

Objective: To describe pill burden before and after hepatitis C virus (HCV) treatment initiation among patients newly treated for HCV infection, and to evaluate the association between HCV pill burden and gaps in HCV therapy.Methods: This was a retrospective administrative claims study of patients treated with direct-acting antivirals (DAAs) for HCV from 1 November 2013 to 31 July 2016. HCV pill burden was defined as the pill count per day for the index HCV regimen. Mean overall pill burden (HCV medications plus non-HCV medications) was calculated in the 90 days before and after DAA initiation. Gaps in the index HCV regimen were assessed in the 6 months after DAA initiation. Multivariable logistic regression was used to compare the odds of a gap in HCV therapy across HCV pill burden categories (1 pill/day, 2 pills/day, and ≥3 pills/day).Results: Among 9815 patients who met the study criteria, mean overall pill burdens before and after DAA treatment initiation were 5.4 and 7.7, respectively (p < .001). The adjusted odds ratio (OR) of a ≥15-day gap in HCV therapy was 1.75 (95% confidence interval [CI] = 1.38–2.22) for patients with 2 HCV pills/day and 2.11 (95% CI = 1.78–2.51) for patients with ≥3 pills/day, compared with patients with 1 HCV pill/day.Conclusions: Patients with HCV have a substantial pill burden even before initiating HCV treatment. As higher HCV pill burden was associated with lower medication adherence, pill burden should be an important consideration in HCV treatment selection.

An Evaluation of Hepatitis C Virus Telehealth Services Serving Tribal Communities: Patterns of Usage, Evolving Needs, and Barriers

American Indian/Alaska Native (AI/AN) populations are disproportionately affected by chronic hepatitis C virus (HCV) infection. Federal facilities of the Indian Health Service, in conjunction with Tribally operated and Urban Indian (I/T/U) health care facilities, serve an estimated 2.2 million AI/AN patients. The facilities are mainly rural and have few specialists. To fill the gap in specialists in I/T/U clinics, the Extension for Community Healthcare Outcomes (ECHO) telehealth model was used to support clinicians to treat HCV in primary care. Participants in 3 regional HCV ECHO networks serving AI/AN patients were surveyed by e-mail and text message to determine patterns of ECHO usage, usefulness, and barriers to treating patients with HCV at their primary care clinics. From a total of 44 respondents from 72 eligible health care facilities, a majority (61%) stated that they started treating patients with HCV subsequent to participating in the telehealth program. Participants with more telehealth experience sought increasing complexity in patient case presentations. In California, 7 of 8 clinicians who had attended more than 10 ECHO sessions expressed diminishing need for ECHO sessions to manage cases (<25% of patients). All elements of the ECHO sessions (presenting patient cases, listening to patient case presentations, teaching sessions, and sharing of programmatic insights) were considered "extremely useful" by the majority of respondents. The factors most cited as moderate or extensive barriers to providing HCV care were access to HCV direct acting antivirals (60%) and linking patients to care (50%). Extension for Community Healthcare Outcomes may play a key role not only in increasing clinical capacity for HCV treatment but also in the inception of HCV services in this sample of I/T/U facilities. Participants with more telehealth experience demonstrated signs of increasing clinical capacity, where they were more likely to seek complex patient case presentations in ECHO sessions. A number of barriers continue to keep AI/ANs from being cured and stop clinicians from ending the epidemic, including access to HCV medications, time to provide HCV clinical services, and linking patients to HCV services.

Automated Text Messaging With Patients in Department of Veterans Affairs Specialty Clinics: Cluster Randomized Trial.

BackgroundAcceptability of mobile phone text messaging as a means of asynchronous communication between health care systems and patients is growing. The US Department of Veterans Affairs (VA) has adopted an automated texting system (aTS) for national rollout. The aTS allows providers to develop clinical texting protocols to promote patient self-management and allows clinical teams to monitor patient progress between in-person visits. Texting-supported hepatitis C virus (HCV) treatment has not been previously tested.ObjectiveGuided by the Practical, Robust Implementation and Sustainability Model (PRISM), we developed an aTS HCV protocol and conducted a mixed methods, hybrid type 2 effectiveness implementation study comparing two programs supporting implementation of the aTS HCV protocol for medication adherence in patients with HCV.MethodsSeven VA HCV specialty clinics were randomized to usual aTS implementation versus an augmented implementation facilitation program. Implementation process measures included facilitation metrics, usability, and usefulness. Implementation outcomes included provider and patient use of the aTS HCV protocol, and effectiveness outcomes included medication adherence, health perceptions and behaviors, and sustained virologic response (SVR).ResultsAcross the seven randomized clinics, there were 293 facilitation events using a core set of nine implementation strategies (157 events in augmented implementation facilitation, 136 events in usual implementation). Providers found the aTS appropriate with high potential for scale-up but not without difficulties in startup, patient selection and recruitment, and clinic workflow integration. Patients largely found the aTS easy to use and helpful; however, low perceived need for self-management support contributed to high declination. Reach and use was modest with 197 patients approached, 71 (36%) enrolled, 50 (25%) authenticated, and 32 (16%) using the aTS. In augmented implementation facilitation clinics, more patients actively used the aTS HCV protocol compared with usual clinic patients (20% vs 12%). Patients who texted reported lower distress about failing HCV treatment (13/15, 87%, vs 8/15, 53%; P=.05) and better adherence to HCV medication (11/15, 73%, reporting excellent adherence vs 6/15, 40%; P=.06), although SVR did not differ by group.ConclusionsThe aTS is a promising intervention for improving patient self-management; however, augmented approaches to implementation may be needed to support clinician buy-in and patient engagement. Considering the behavioral, social, organizational, and technical scale-up challenges that we documented, successful and sustained implementation of the aTS may require implementation strategies that operate at the clinic, provider, and patient levels.Trial RegistrationRetrospectively registered at ClinicalTrials.gov NCT03898349; https://clinicaltrials.gov/ct2/show/NCT03898349

Adoption of direct-acting antiviral medications for hepatitis C: a retrospective observational study

BackgroundApproximately 3.5 million Americans are infected with the hepatitis C virus (HCV). Although many patients with HCV are asymptomatic, HCV is the leading cause of infection-related death in the U.S. With advances in curative medication therapy for HCV, many of these deaths are preventable. Access to innovative therapies may be unevenly distributed. Our objective was to describe medication prescribers’ adoption of innovative HCV pharmacotherapy across prescriber, geographical location, and time.MethodsThis is a retrospective, secondary data analysis among a national cohort of patients prescribed direct-acting antiviral HCV medications with curative intent. We assessed prescriptions by time, geographic location, and provider type.ResultsThe peak of the adoption rate occurred within 45 days; nearly one-sixth of all prescribers had already prescribed one of the new drugs. Geographical regions (Midwest, South, and West all p ≥ 0.05) nor gender (p = 0.455) of a prescriber impacted adoption. Similarly, patient income did not influence the likelihood of a prescriber to adopt the new drugs earlier (p = 0.175). Gastroenterologists or hepatologists were more likely earlier adopters compared to primary care physicians (p = 0.01).ConclusionsBecause of the relative advantage of newer therapies, we anticipated that there would be an initial surge as early adopters prescribed the new medications and use would dwindle over time as the initial HCV cohort was cured. The data demonstrate that our hypothesis is essentially supported. There is a reduction in prescriptions at approximately 5 months post-approval and treatment is typically required for 3 months. There has been a surge in clinicians’ adoption of innovative HCV treatments. As patients are cured of their infection, we anticipate a decreased need for chronic management of HCV.Trial registrationNot applicable.KeywordsDissemination researchHealth services researchInfectious diseaseHepatitis C

Evaluation of Safety and Effectiveness of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch Followed by Ledipasvir/Sofosbuvir HCV Therapy in HIV-HCV Coinfection.

BackgroundWe conducted a pilot study assessing the feasibility, efficacy, and safety of a simplified combination HIV antiretroviral and hepatitis C virus (HCV) antiviral regimen in HIV–HCV coinfection.MethodsParticipants on suppressive antiretrovirals and HCV genotype 1 infection were switched to single-tablet daily-dosed elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) and 1 month later initiated single-tablet-regimen daily-dosed ledipasvir-sofosbuvir for 12 weeks. E/C/F/TAF was continued during HCV treatment and for 12 weeks after.ResultsTwenty-six individuals were screened, 25 enrolled, and 23 completed all HIV and HCV treatment. Participants were predominantly male, with a mean age (SD) of 55 (7.5) years. The median transient elastography score (interquartile range [IQR]) was 5.9 (5.3 to 7.6) kPa, and the mean CD4 count (SD) was 579 (223) cells/µL. The median adherence to HCV medications, assessed by pill count, was 100% (95% confidence interval [CI], 100%–100%), and HIV ranged from 99% to 100% (100%; 95% CI, 90%–100%) over the 7-month study duration. HIV undetectability was maintained in all but 1 participant enrolled with unsuspected multiclass resistance. Treatment was well tolerated, with no study medication modification due to adverse events and no serious adverse event related to the study drug. All participants achieved sustained virological response. The mean CD4 count (SD) increased to 673 (361) cells/µL, and the fibrosis score (IQR) declined to 5.2 (4.4 to 7.4) kPa by week 12 after HCV treatment. There was no treatment effect on glucose metabolism. Cholesterol increased during and after treatment.ConclusionsProvision of this 2-tablet daily HIV–HCV regimen is feasible, well tolerated, and safe, avoids drug–drug interactions between HIV and HCV medications, maintains HIV suppression in the absence of drug resistance, and is highly curative of HCV.

PIN79 ACCESS TO HCV CURE UNDER MEDICAID PROGRAMS IN THE UNITED STATES

Restrictive policies on access to new, curative hepatitis C virus (HCV) treatments represent a substantial barrier to care. In this study, we evaluated the access rates to HCV treatment for Medicaid patients in 27 States in 2016-2017. Data were collected using Trio Health’s disease management program and are specific to Medicaid-insured patients prescribed anti-HCV therapy in 2016-2017. Access was defined as dispensed direct-acting antivirals (DAA). Access rates were only calculated for sample sizes of >30 patients. To determine dispense, patients were followed for 150+ days from prescription date. Cirrhotic status was assigned based on physician-reported fibrosis scores. Of the total HCV Medicaid subjects in the cohort, 3802/5493 (69%) had access to treatment. In the 27 States evaluated, 9 States had 2-year access rates <50%, 10 had rates of 50%-70%, and 8 had rates >70%. In 11 States with sufficient cirrhotic (F4) and non-cirrhotic samples (F0-3), access rates were higher in each State for patients with cirrhosis. The greatest disparities between F0-3 and F4 were observed for Idaho (56% access F0-3 vs. 84% access F4) and California (60% access F0-3 vs. 83% access F4). Smallest differences between F0-3 and F4 were observed for Washington (93% access F0-3 vs. 95% access F4) and Connecticut (96% access F0-3 vs. 100% access F4). Year over year changes were assessed for 18 States: access rates increased in 15 States, decreased in 2 States, and remained flat for 1 State. Despite a decrease in the price of HCV medications, access to HCV treatment remains a barrier to reducing HCV-associated morbidity and mortality. Prioritization of care appears to remain, with many States displaying higher access rates for patients with cirrhosis compared to non-cirrhotic patients.

Primary care provider perceptions and experiences of implementing hepatitis C virus birth cohort testing: a qualitative formative evaluation

BackgroundIn 2014, the Department of Veterans Affairs (VA) adopted a screening test policy for hepatitis C virus (HCV) in all “Baby Boomers” - those born between 1945 and 1965. About 1 in 12 Veterans were estimated to be infected with HCV yet approximately 34% of the birth cohort remained untested. Early HCV diagnosis and successful antiviral treatment decrease the risk of onward transmission, cirrhosis, hepatocellular carcinoma, liver transplant, and death. Implementing evidence-based HCV screening in primary care has great potential to reduce morbidity and mortality. To inform design and implementation of a quality improvement intervention, we studied primary care provider (PCP) perceptions of and experiences with HCV birth cohort testing.MethodsWe conducted a formative evaluation using qualitative semi-structured interviews guided by the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework. Twenty-two PCPs in six states across a large integrated US healthcare system were interviewed. Content analysis with a priori and emergent codes was performed on verbatim interview transcripts.ResultsWe identified three themes related to primary care provider HCV testing and linkage practices, as mapped to i-PARIHS constructs: 1) evaluating cues to HCV testing (innovation/evidence), 2) framing HCV testing decisions (recipients), and 3) HCV testing and linkage to care in the new treatment era (context). The most frequently reported HCV testing cue was an electronic clinical reminder alert, followed by clinical markers and the presence of behavioral risk factors. Most PCPs saw testing as routine, but less urgent, leading to some reluctance. Providers largely saw themselves as performing guideline-concordant testing, yet no performance data were available to assess performance. Given the recent availability of new HCV medications, many PCPs were highly motivated to test and link patients to specialty care for treatment.ConclusionsOur results suggest a multi-component intervention around awareness and education, feedback of performance data, clinical reminder updates, and leadership support, would address both a significant need, and be deemed acceptable and feasible to primary care providers.

Direct-acting antiviral hepatitis C virus treatment perturbation of the metabolic milieu

Hepatitis C virus (HCV), cirrhosis, and HCV medications including direct-acting antivirals (DAAs) ±ribavirin may all influence the metabolic milieu. While interferon-based regimens improve glucose tolerance, evidence is limited on DAAs. Cases of elevated lactate have recently been reported in patients treated with DAAs, and lactic acidosis is a known complication of antivirals used to treat hepatitis B virus and HIV. Measures were evaluated at baseline, week 4, end of treatment, and 12-24 weeks after treatment. Mixed-effects modeling was used to determine factors influencing glucose and lactate over time. In total, 442 patients were treated (mean age 56, 65% male, 72% genotype 1, 48% cirrhotic). Glucose did not change on or after DAA treatment from baseline (P=0.51) aside from those with untreated diabetes, which declined (P=0.02). Overall, there was a decline in lactate following HCV treatment (mean 2.4-2.1 mmol/l; P<0.001). Lactate initially increased on treatment and then decreased after treatment completion in male patients treated with ribavirin. This pattern was not observed in other groups. There was no evidence of lactic acidosis with HCV nucleotide use. Distinct glucose and lactate trajectories were identified without evidence of DAA metabolic toxicity. HCV treatment does not improve random glucose levels aside from perhaps in untreated diabetic patients.

Real-world effectiveness of daclatasvir plus sofosbuvir and velpatasvir/sofosbuvir in hepatitis C genotype 2 and 3

Understanding the real-world effectiveness of all-oral hepatitis C virus (HCV) regimens informs treatment decisions. We evaluated the effectiveness of daclatasvir + sofosbuvir ± ribavirin (DCV + SOF ± RBV) and velpatasvir/sofosbuvir (VEL/SOF) ± RBV in patients with genotype 2 and genotype 3 infection treated in routine practice. This observational analysis was carried out in an intent-to-treat cohort of patients with HCV genotype 2 and genotype 3. Sustained virologic response (SVR) analysis was performed in 5,400 patients initiated on DCV + SOF ± RBV or VEL/SOF ± RBV at any Department of Veterans Affairs facility. For genotype 2, SVR rates did not differ between DCV + SOF (94.5%) and VEL/SOF (94.4%) or between DCV + SOF + RBV (88.1%) and VEL/SOF + RBV (89.5%). For genotype 3, SVR rates did not differ between DCV + SOF (90.8%) and VEL/SOF (92.0%) or between DCV + SOF + RBV (88.1%) and VEL/SOF + RBV (86.4%). In multivariate models of patients with genotype 2 and 3 infection, the treatment regimen was not a significant predictor of the odds of SVR. For genotype 3, significant predictors of reduced odds of SVR were prior HCV treatment-experience (odds ratio [OR] 0.51, 95% CI 0.36-0.72; p <0.001), FIB-4 >3.25 (OR 0.60; 95%CI 0.43-0.84; p = 0.002) and a history of decompensated liver disease (OR 0.68; 95%CI 0.47-0.98; p = 0.04). For patients with genotype 2 and 3, treated with VEL/SOF ± RBV, 89% and 85% received 12-weeks of treatment, respectively. For DCV + SOF ± RBV, 56% and 20% of patients with HCV genotype 2 received 12-weeks and 24-weeks of treatment, respectively; while 53% and 23% of patients with HCV genotype 3 received 12-weeks and 24-weeks, with most direct-acting antiviral experienced patients receiving 24-weeks. In patients infected with HCV genotype 2 and 3, DCV + SOF ± RBV and VEL/SOF ± RBV produced similar SVR rates within each genotype, and the regimen did not have a significant impact on the odds of SVR. For patients with genotype 3, prior treatment-experience and advanced liver disease were significant predictors of reduced odds of SVR regardless of regimen. In clinical practice, cure rates for hepatitis C virus (HCV) genotype 2 were 94% and cure rates for HCV genotype 3 were 90%. The chance of achieving cure was the same whether a person received daclatasvir plus sofosbuvir or velpatasvir/sofosbuvir. Ribavirin did not affect cure rates. The chance of a cure was lowest in people who had received HCV medication in the past.

Role of a clinical pharmacist as part of a multidisciplinary care team in the treatment of HCV in patients living with HIV/HCV coinfection.

BackgroundThe objective of the study was to evaluate the role of a clinical pharmacist in hepatitis C virus (HCV) treatment of patients living with HIV/HCV coinfection.MethodsWe conducted a descriptive study to quantify the functions of a clinical pharmacist in HCV treatment of patients living with HIV/HCV coinfection who were initiating HCV treatment at a publicly funded clinic between March 18, 2015 and September 15, 2016. The clinical pharmacist’s role was categorized into eight categories: 1) HCV prior authorization (PA) completion; 2) HCV medication adherence counseling; 3) HCV drug-drug interaction (DDI) counseling and screening; 4) HCV medication counseling regarding common adverse events (AEs); 5) HCV counseling regarding HCV treatment outcomes and risk of reinfection; 6) ordering laboratory tests and interpretation of HCV laboratory values; 7) HIV medication AE assessment; and 8) other (including refilling medications and management of other comorbidities).ResultsOne hundred and thirty-five patients initiated treatment during this timeframe: 77.0% were males, 56.3% non-cirrhotic, 77.0% HCV treatment-naïve, 45.9% HCV genotype 1a, and 83.0% initiated on ledipasvir/sofosbuvir. The clinical pharmacist completed 150 PAs, counseled on HCV medication adherence in 79.2% of patients, conducted HCV DDI counseling and screening in 54.2%, and monitored HCV medication AEs in 54.2%. The clinical pharmacist counseled patients on HCV treatment outcomes and risk of reinfection in 53.1%, ordered laboratory tests in 44.8%, and reported and interpreted laboratory values in 44.8%. The clinical pharmacist assessed HIV medication AEs in 54.2% of patients and participated in other activities in 42.7%.ConclusionA clinical pharmacist’s expertise as part of a multidisciplinary care team facilitates optimal treatment outcomes and provides critical support in the management of DAA therapy in individuals living with HIV/HCV coinfection.

Accepting hepatitis C virus-infected donor hearts for transplantation: Multistep consent, unrealized opportunity, and the Stanford experience.

The current mismatch between supply and demand of organs has prompted transplant clinicians to consider innovative solutions to broaden the donor pool. Advancements of direct-acting antiviral agent (DAA) therapy for hepatitis C virus (HCV) have allowed entertaining the use of viremic donor organs in nonviremic recipients. In this report, we describe the evolution of HCV treatment, ethics and informed consent, cost-effectiveness of HCV medications in treating acute HCV post-transplantation, and the Stanford experience with two HCV-viremic donor heart transplantations. We describe excellent short-term outcomes post-heart transplantation with HCV NAT-positive organs. The availability of this therapy may expand the donor pool. While we await larger-scale clinical data on the effectiveness and safety of DAA therapy in patients after heart transplantation, many transplant centers have already started accepting organs from HCV-infected donors, balancing the unknown long-term risks versus the benefits of shorter wait times and expansion of the donor pool. Protocols and multidisciplinary teams are needed to effectively communicate risk to potential recipients, to ensure timely DAA access, and to implement appropriate clinical follow-up in order to achieve excellent clinical outcomes and to maximize the donor pool by utilizing HCV-infected organs for heart transplantation.

A Descriptive Analysis of a Community Clinic Providing Hepatitis C Treatment to Poor and Uninsured Patients.

This study describes clinical characteristics of poor and uninsured patients living with hepatitis C virus (HCV) who received care from a multidisciplinary HCV clinic, reports treatment completion and cure rates, and estimates the cost of HCV medications provided at no cost to uninsured patients. A retrospective chart review was performed and identified 69 uninsured HCV patients who received medical care at Mercy Health Center, a small non-profit community clinic, between January 2008 and March 2015. Three-fourths of the patients were unemployed, a third had multiple HCV exposures, nearly half acquired HCV due to illicit drug use, and more than half had active psychiatric disorders. Of those who received HCV treatment, 81% completed treatment and 85% were achieved virological cure. The multidisciplinary community clinic provided > $1.4million of HCV antivirals at no cost to uninsured patients. Findings suggest a multidisciplinary community clinic comprised of a social worker, pharmacist, gastroenterologist, nurse, nurse practitioner, psychologist, and dietitian can help patients achieve HCV treatment completion and cure rates comparable to traditional physician-led clinics, and successfully manage uninsured and underserved HCV patients-who are often regarded as "difficult-to-treat" patients. Public health social workers and other health professionals are encouraged to advocate for treatment and care of poor and uninsured patients living with HCV in health agencies and health systems, otherwise population-wide reductions in HCV morbidity and mortality will not be realized.

Improving patient access to hepatitis C virus treatment

ObjectivesTo discuss the current barriers to hepatitis C virus (HCV) treatment; to provide information and resources to assist health care providers with the prior authorization process; to provide resources for potential access to medications if a patient's third-party payer may not be an option; and to discuss the pharmacist's vital role as a patient advocate and considerations once medications are approved. SummaryAccess to HCV medications is often restricted by third-party payers. Pharmacists are poised to fill an immediate need and assist with providing the necessary clinical evidence to gain access to HCV medications and advocate on the patient's behalf. Once approval for HCV treatment has been obtained, considerations must be given to procurement of therapy, refills, monitoring, and avoid interruptions in therapy. ConclusionThe assistance of a pharmacist should be sought to overcome barriers related to medication access. Once therapy has been obtained, the pharmacist can assist the entire patient care team to ensure timely refills, appropriate monitoring, tolerability of therapy, and continued medication access.

Evaluating a Collaborative Approach to Improve Prior Authorization Efficiency in the Treatment of Hepatitis C Virus.

Objective:A team-based approach to obtaining prior authorization approval was implemented utilizing a specialty pharmacy, a clinic-based pharmacy technician specialist, and a registered nurse to work with providers to obtain approval for medications for hepatitis C virus (HCV) infection. The objective of this study was to evaluate the time to approval for prescribed treatment of HCV infection.Methods:A retrospective observational study was conducted including patients treated for HCV infection by clinic providers who received at least 1 oral direct-acting antiviral HCV medication. Patients were divided into 2 groups, based on whether they were treated before or after the implementation of the team-based approach. Student t tests were used to compare average wait times before and after the intervention.Results:The sample included 180 patients, 68 treated before the intervention and 112 patients who initiated therapy after. All patients sampled required prior authorization approval by a third-party payer to begin therapy. There was a statistically significant reduction (P = .02) in average wait time in the postintervention group (15.6 ± 12.1 days) once adjusted using dates of approval.Conclusions:Pharmacy collaboration may provide increases in efficiency in provider prior authorization practices and reduced wait time for patients to begin treatment.

A Hepatitis C Treatment Program Based in a Safety-Net Hospital Patient-Centered Medical Home.

Hepatitis C virus (HCV) infection is a major public health problem. Urban safety-net hospitals are a prime location for HCV treatment delivery. Showing that physicians in primary care settings can deliver HCV infection care is important to expand treatment; models doing so in the era of newer oral HCV medications are needed. This article describes an innovative and successful HCV primary care treatment program in a patient-centered medical home based at an urban, safety-net hospital. The program is public health oriented in that a central team member is a public health social worker who performs population management and addresses underlying social determinants of health to facilitate engagement in HCV treatment. Other team members include general internists trained to treat HCV infections, a pharmacist, and a pharmacy technician. The program is funded with revenue generated by the 340b drug discount program, which allows providers to generate revenue when patients fill prescriptions at pharmacies in safety-net settings, as insurance reimbursements for medications exceed the cost at which safety-net providers purchase medications. During the course of 1 year, the program received 302 referrals. Of these approximately 23% have received treatment.

HCV management in resource-constrained countries.

With the arrival of all-oral directly acting antiviral (DAA) therapy with high cure rates, the promise of hepatitis C virus (HCV) eradication is within closer reach. The availability of generic DAAs has improved access to countries with constrained resources. However, therapy is only one component of the HCV care continuum, which is the framework for HCV management from identifying patients to cure. The large number of undiagnosed HCV cases is the biggest concern, and strategies to address this are needed, as risk factor screening is suboptimal, detecting <20% of known cases. Improvements in HCV confirmation through either reflex HCV RNA screening or ideally a sensitive point of care test are needed. HCV notification (e.g., Australia) may improve diagnosis (proportion of HCV diagnosed is 75%) and may lead to benefits by increasing linkage to care, therapy and cure. Evaluations for cirrhosis using non-invasive markers are best done with a biological panel, but they are only moderately accurate. In resource-constrained settings, only generic HCV medications are available, and a combination of sofosbuvir, ribavirin, ledipasvir or daclatasvir provides sufficient efficacy for all genotypes, but this is likely to be replaced with pangenetypic regimens such as sofosbuvir/velpatasvir and glecaprevir/pibrentaasvir. In conclusion, HCV management in resource-constrained settings is challenging on multiple fronts because of the lack of infrastructure, facilities, trained manpower and equipment. However, it is still possible to make a significant impact towards HCV eradication through a concerted effort by individuals and national organisations with domain expertise in this area.

Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions.

AIMTo quantify drug-drug-interactions (DDIs) encountered in patients prescribed hepatitis C virus (HCV) treatment, the interventions made, and the time spent in this process.METHODSAs standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral (DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir (LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir (OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTSSix hundred and sixty four patients (83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients.CONCLUSIONDDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care.

Real-World Drug Costs of Treating Hepatitis C Genotypes 1-4 with Direct-Acting Antivirals: Initiating Treatment at Fibrosis 0-2 and 3-4.

Direct-acting antivirals (DAA) for the treatment of hepatitis C virus (HCV) have drastically improved outcomes but are also very costly. For this reason, priority for treatment is often given to patients with a higher fibrosis score at baseline by payers and providers rather than treating all eligible patients. Simulation studies have suggested that waiting to treat patients until fibrosis 3-4 may be more costly and result in worse outcomes; however, real-world implications are unknown. To determine drug costs and outcomes for treating hepatitis C in patients with fibrosis scores of 0-2 and 3-4 at baseline in a real-world ambulatory care setting. A total of 322 patients at 36 clinical sites in Massachusetts with HCV genotype 1-4 and a prescription for at least 1 DAA medication between May 2011 and October 2015 were included. Retrospective and prospective chart reviews were completed by the primary investigator. Data were collected through April 2016. The primary outcome for the study was to determine the mean drug cost per sustained virologic response (SVR) achieved for patients with fibrosis scores of 0-2 and 3-4. Drug costs were calculated using average wholesale price and only included the cost of HCV medications, not for adjunctive medications, blood work, hospitalizations, anticipated complications, or any other projected medical costs. The mean ± SD (median) drug cost per patient was $130,391 ± 46,787 (113,400) and completed treatment duration was 15.0 ± 8.9 (12) weeks. The mean drug cost per SVR was $155,662 for all patients with a mean drug cost per SVR of $122,452 and $178,401 for patients with fibrosis scores of 0-2 and 3-4, respectively. SVR rates were 83.5% (269/322) for all patients and 92.2% (107/116) and 78.6% (162/206) for patients with fibrosis scores of 0-2 and 3-4, respectively. Ledipasvir/ sofosbuvir; sofosbuvir + ribavirin; ledipasvir/sofosbuvir + ribavirin; sofos-buvir + interferon + ribavirin; boceprevir + interferon + ribavirin; sofosbu-vir + simeprevir; and telaprevir + interferon + ribavirin had a mean drug cost per SVR of $123,559; $153,347; $157,969; $184,800; $248,640; $251,550; and $373,333; respectively. Real-world knowledge about outcomes and drug costs may influence future decisions. Further studies are needed to evaluate emerging treatment options and to reflect changes in treatment guidelines. No outside funding supported this study. The authors report no conflicts of interest. Data in this study were presented as a poster at the ASHP Midyear Clinical Meeting; New Orleans, Louisiana; December 9, 2015; at the Massachusetts Society of Health-System Pharmacists Annual Meeting; Newton, Massachusetts; April 12, 2016; and at Eastern States Conference for Pharmacy Residents and Preceptors; Hershey, Pennsylvania; May 2, 2016. Study concept and design was primarily contributed by Bach, along with Zaiken. Bach took the lead in data collection, data interpretation, and preparation of the manuscript, along with Zaiken.

Overview of Comprehensive Hepatitis C Virus Medication Management in a State Medicaid Program.

Breakthrough direct-acting antivirals set a new standard in the management of hepatitis C virus (HCV) with regard to cure rates and improved tolerability; however, the health care system is challenged by the cost of these medications. To describe the effect of a comprehensive HCV medication management program on optimized regimen use, prior authorization (PA) modifications, and medication cost avoidance in a state Medicaid program. This program consists of a 2-tiered prescriber outreach: (1) regimen outreach to promote optimized regimen selection and (2) refill outreach to support medication adherence. PA criteria were developed to identify optimized regimens, taking into account member- and virus-specific factors as well as cost. Prescriber outreach was conducted to recommend the use of an optimized regimen as applicable. Successful regimen outreach was defined as the number of members for whom a recommendation was accepted. A refill report identified members without a subsequent paid HCV medication claim within 25 days of the previous claim and outreach to the prescriber's office was performed. The outcome measure for refill outreach was the number and type of PA modifications made secondary to outreach (closure or extension). Cost avoidance was calculated for members who completed treatment with an optimized regimen. Return on investment (ROI) was calculated for the program. Between December 18, 2013, and January 31, 2015, 911 members had PA requests approved for simeprevir, sofosbuvir, or ledipasvir/ sofosbuvir. Of these members, 223 (24.5%) met the criteria for regimen outreach. Pharmacist interventions to treat with an optimized regimen were accepted for 135 members (60.5%). Following implementation of prescriber outreach to promote refills, between March 10, 2014, and January 31, 2015, offices were informed of an upcoming refill for 515 members. As a result of outreach, 19.6% of members had a subsequent PA modification. Sixty-nine approved PAs (for 68 members) were closed after correspondence with the prescriber, and 33 approved PAs (for 33 members) were extended. The total projected cost avoidance was $3,770,097. The comprehensive HCV medication management program demonstrated an ROI of $10.28 for every $1 spent. A comprehensive HCV medication management program can help contain costs while ensuring that members have access to most clinically appropriate regimens. No outside funding supported this study. Lavitas reports personal fees and nonfinancial support from University of Tennessee, Advanced Studies in Medicine and grant funding from Bristol-Myers Squibb, outside the submitted work. All other authors report no conflicts of interest. The poster "Overview of a Hepatitis C Medication Monitoring Program in a State Medicaid Program" was presented October 8, 2014, by Lavitas at the AMCP Nexus 2014 meeting in Boston, Massachusetts. A program update was presented at the 2015 American Drug Utilization Review Society Meeting on February 27, 2015. Study concept and design were contributed by Price, Lenz, and Jeffrey, with assistance from Lavitas, Tesell, and Hydery. Lavitas, Tesell, and Hydery collected the data, assisted by Price, Lenz, and Jeffrey, and data interpretation was performed by all authors. The manuscript was written by Greenwood, Lavitas, Tesell, and Hydery, with assistance from the other authors, and was revised by all authors.

Development of a specialty medication prior-authorization service at an urban academic medical center.

The project in which a clinical pharmacist enlisted the help of pharmacy students to create a team responsible for prior-authorization (PA) paperwork associated with hepatitis C virus (HCV) infection treatment is described. Many insurance companies require completion of a time-consuming PA process for approval of high-cost specialty medications, such as those used in the treatment of HCV infection. A clinical pharmacist at an urban academic medical center recruited pharmacy students to assist with and streamline the HCV medication PA process. After training, the students developed a protocol to increase the efficiency of completing PA requests, appealing denials, obtaining PA extensions, and documenting progress in the electronic medical record to ensure continuity of care. The PA team collaborated with clinicians to document proof of medical need and worked with insurers, pharmacies, and patients to achieve timely approval and receipt of medications. From June 2014 to March 2015, three students spent 240 hours developing the PA protocol and completing 88 PA requests, with an overall medication approval rate of 87.7%; 18 patients were also referred to medication assistance programs. The PA team's work allowed the clinical pharmacist to spend more time on clinical activities and scholarship, while the students increased their knowledge of HCV disease and HCV-targeted therapies and improved their skills in written and verbal communication with patients, providers, and insurance companies. Pharmacy students successfully implemented a PA team to manage prescription approval for HCV medications with assistance from a clinical pharmacist.