Marisel Segarra-Newnham is an Infectious Diseases Clinical Pharmacy Specialist; at the time of the project, Nathalie See was a Pharmacy Resident; and Gail Fox-Seaman is a Nurse Practitioner; all at the West Palm Beach Veterans Affairs Medical Center in Florida. Nathalie See is a Post Graduate Year 2 Pharmacy Practice Resident at University of Florida Health Jacksonville. Correspondence: Marisel Segarra-Newnham (marisel.segarra-newnham @va.gov)
Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Background: Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) results in sustained virologic response (SVR) in > 90% of patients. However, some patients required retreatment with newer DAA options. Treatment was selected after consultation with a clinical pharmacy specialist.
Methods: A retrospective chart review of patients at the West Palm Beach Veterans Affairs Medical Center (WPBVAMC) in Florida retreated from January 2015 to December 2019 was conducted. Data collected included HCV genotype, previous therapy, newly prescribed medications, and treatment outcomes.
Results: Since 2015, > 900 patients have been treated at WPBVAMC, including 22 patients who had previously failed interferon combined with DAA regimens and 46 patients who needed retreatment after failure with an all-oral therapy. This review documents the outcomes of retreatment with DAA after initial failure to achieve SVR Of 28 patients treated with a boceprevir-based regimen, 10 ended in failure. All 10 were retreated, and all achieved SVR with ledipasvir/sofosbuvir. Of 53 patients treated with a sofosbuvir-based interferon regimen, 12 failed treatment. All 12 were retreated and all achieved SVR. Thirty patients were retreated after failure with an all-oral DAA. Of 27 tested, 21 achieved SVR. All patients who failed therapy again had cirrhosis.
Conclusions: Veterans retreated with DAAs for HCV infection had a high success rate. Repeat failures of DAAs were rare, but cirrhosis seems to be common among these patients.
An estimated 3.5 million people in the US have chronic hepatitis C virus (HCV) infection, and between 10% and 20% of those developed cirrhosis over 20 to 30 years.1 There are at least 6 genotypes (GTs) of HCV, with GT1 being the most common in the US and previously one of the most difficult to treat.2,3 The goal of treatment is to achieve viral cure, called sustained virologic response (SVR) when HCV viral load remains undetectable several weeks after therapy completion. In the 2000s, pegylated interferon (pegIFN) and ribavirin (RBV) were the standard of care.2 For patients with GT1 infections, an SVR of 40 to 50% was commonly seen after 48 weeks of pegIFN/RBV regimens compared with 70 to 80% SVR for GT2 or GT3 after 24 weeks of pegIFN/RBV therapy.2 However, treatment has evolved rapidly (Table 1).2-17
In 2011, the US Food and Drug Administration (FDA) approved the protease inhibitors (PIs) boceprevir and telaprevir, which added a new class of agents with increased SVR for patients with GT1 infection; however, pegIFN and RBV were still needed for treatment.4 In addition, both PIs required multiple doses per day and strict adherence to an 8-hour schedule.4 Boceprevir required treatment with RBV and pegIFN for 48 weeks unless futility rule was met at 24 weeks of treatment (ie, viral load still detectable).4 The SVR in patients with GT1 infection improved to > 65% for patients in clinical trials.2 FDA approval of the direct-acting antivirals (DAAs) sofosbuvir and simeprevir in late 2013 decreased the usual duration of therapy to only 12 weeks with improved SVR rates 12 weeks posttherapy (SVR12) to 90% or higher.2,6,10
FDA approval of ledipasvir (LDV)/sofosbuvir (SOF) in October 2014 resulted in the first interferon-free all-oral regimen indicated for HCV GT1 infection.11 In December 2014, FDA approved a combination of paritaprevir, ritonavir, ombitasvir, and dasabuvir (PrOD).12 In 2015 GT-specific approvals were issued for daclastavir to be used with SOV for GT1 and GT3 and a combination similar to PrOD without dasabuvir (PrO) for GT4.13 In 2016, a combination of elbasvir (ERB) and grazoprevir (GZP) was approved for GT1 and GT4.14
In 2016, a pangenotypic DAA of SOF and velpatasvir (VEL) was approved.15 Most recently, combinations of SOF, VEL, and voxilaprevir (VOX), and glecaprevir (GLE) and pibrentasvir (PIB) were approved for patients with previous DAA treatment failures.7, 8,16,17 These oral regimens avoided the significant adverse events (AEs) associated with pegIFN and RBV (eg, thrombocytopenia, depression), were expected to improve treatment adherence and shorten duration of therapy.
The West Palm Beach Veterans Affairs has had a nurse practitioner (NP)-based HCV treatment clinic since the late 1990s. When PIs became available, a CPS started reviewing patient electronic health records (EHRs) and monitored response to therapy along with the NP to ensure discontinuation of therapy if futility criteria were met.7 Our unpublished experience showed SVR > 60% with both boceprevir and SOF regimens and > 90% with oral DAA regimens.
This review will provide the SVR rates for patients that needed retreatment for HCV infection since 2015 until December 2019. We treated all willing patients, beginning with the patients who had experienced failures with previous regimens. Patients first received education on HCV infection and treatment options in a group class then they were seen by the NP individually for specific education on treatment. The CPS reviewed the patient’s medical record to assess for appropriate therapy, possible drug-drug interactions and contraindications to therapy. In addition, patient outcomes (eg, viral load, AEs) were documented by the CPS in collaboration with the NP throughout treatment until viral load for SVR evaluation was obtained.
