• CDC
  • Heart Failure
  • Cardiovascular Clinical Consult
  • Adult Immunization
  • Hepatic Disease
  • Rare Disorders
  • Pediatric Immunization
  • Implementing The Topcon Ocular Telehealth Platform
  • Weight Management
  • Monkeypox
  • Guidelines
  • Men's Health
  • Psychiatry
  • Allergy
  • Nutrition
  • Women's Health
  • Cardiology
  • Substance Use
  • Pediatrics
  • Kidney Disease
  • Genetics
  • Complimentary & Alternative Medicine
  • Dermatology
  • Endocrinology
  • Oral Medicine
  • Otorhinolaryngologic Diseases
  • Pain
  • Gastrointestinal Disorders
  • Geriatrics
  • Infection
  • Musculoskeletal Disorders
  • Obesity
  • Rheumatology
  • Technology
  • Cancer
  • Nephrology
  • Anemia
  • Neurology
  • Pulmonology

Newer Hepatitis C Drugs Mean Direct Action

Article

The “modern era” of treatment features multiple DAAs that target specific steps within the HCV life cycle.

The “modern” era of hepatitis C virus (HCV) treatment began in 2014 with FDA approval of the direct acting antiviral agent (DAA) Harvoni for use in HCV monoinfected patients. Since then, the FDA-approved indication of Harvoni has been expanded to include the HCV/HIV co-infected population and the FDA has approved 5 more DAAs or combinations of DAAs.

Treatment Regimens Target Proteins[[{"type":"media","view_mode":"media_crop","fid":"58552","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_3111892686213","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7393","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 233px; width: 228px; border-width: 0px; border-style: solid; margin: 5px; float: right;","title":" ","typeof":"foaf:Image"}}]]

The development of multiple DAAs, which target specific steps within the HCV life cycle, has been facilitated by knowledge of the HCV genome and proteins. The current treatment regimens target proteins that are involved in HCV replication and assembly, such as NS3/4A protease, NS5B polymerase, and the NS5A protein. Combination therapy is used to optimize HCV treatment response rates and reduce the likelihood of developing treatment-emergent resistance-associated variants.

Following are the 4 classes of DAAs:

1. NS3/4A protease inhibitors: grazoprevir (a component of Zepatier™), paritaprevir (a component of Technivie™ and Viekira Pak™), and simeprevir (Olysio™).

2. NS5A inhibitors: daclatasvir (Daklinza™), elbasvir (a component of Zepatier™), ledipasvir (a component of Harvoni™), ombitasvir (a component of Technivie™ and Viekira Pak™), and velpatasvir (a component of Epclusa™).

3.NS5B nucleot(s)ide polymerase inhibitors: sofosbuvir (Solvaldi™ and a component of Harvoni™).

4.NS5B non-nucleoside polymerase inhibitors: dasabuvir (a component of Viekira Pak™).

Compensated or Decompensated Cirrhosis?

Duration of treatment is based on genotype, prior treatment history, and the presence of compensated or decompensated cirrhosis. These types of cirrhosis may be distinguished by noting that persons with compensated cirrhosis do not have hepatic encephalopathy, ascites, variceal bleeding, or jaundice. Treatment of patients with decompensated cirrhosis or those with hepatocellular carcinoma should be deferred to a specialist.

Persons who are co-infected with HIV and hepatitis B virus probably should be referred to an infectious diseases specialist or to a hepatologist.

Next: Currently Approved Treatment Regimens

Approved Treatment Regimens for HCV

The currently approved treatment regimens are presented below, in no particular order:

Genotype 1a Treatment Options for Treatment-naive Persons and PEG-IFN/Ribavirin Treatment–experienced Persons

Zepatier™ (elbasvir/grazoprevir daily): duration, 12 weeks. Do not use in patients who have detectable NS5A resistance-associated variants (RAVs) at baseline.

Harvoni™ (ledipasvir/sofosbuvir daily): duration, 12 weeks.    

Viekira Pak™ (paritaprevir/ritonavir/ombitasvir daily plus dasabuvir twice daily) with weight-based ribavirin: duration, 12 weeks. Recommended treatment duration is 24 weeks as an alternative regimen in those with compensated cirrhosis who are PEG-IFN/ribavirin treatment experienced.

Olysio™ (simeprevir daily) plus Sovaldi™ (sofosbuvir daily): duration, 12 weeks. For compensated cirrhosis, the recommended treatment duration is 24 weeks as an alternative regimen with or without the addition of ribavirin. In patients who are PEG-IFN/ribavirin treatment experienced, can be used only in those who are negative for the Q80K variant.

Epclusa™ (sofosbuvir/velpatasvir daily): duration, 12 weeks.  

Sovaldi™ (daclatasvir [Daklinza™]) plus sofosbuvir daily): duration, 12 weeks. For compensated cirrhosis, recommended treatment duration is 24 weeks as an alternative regimen with or without the addition of ribavirin. Dose of daclatasvir may need to be adjusted if patient is on cytochrome P 450 3A/4 inducers or inhibitors.

Zepatier™ (elbasvir/grazoprevir daily) plus weight-based ribavirin: duration, 16 weeks. Alternative regimen for those who have compensated cirrhosis and baseline NS5A RAVs for elbasvir.

► All drugs can be used in patients who have compensated cirrhosis, in patients who are PEG-IFN/ribavirin treatment experienced without cirrhosis, and (other than Sovaldi) in patients who are PEG-IFN/ribavirin treatment experienced with compensated cirrhosis.

Next: Genotype 1b Treatment Options

Genotype 1b Treatment Options for Treatment-naive Persons and PEG-IFN/Ribavirin Treatment– experienced Persons

Zepatier™ (elbasvir/grazoprevir daily): duration, 12 weeks.

Harvoni™ (ledipasvir/sofosbuvir daily): duration, 12 weeks. Duration of treatment in those who are PEG-IFN/ribavirin treatment experienced with compensated cirrhosis is 12 weeks with the addition of weight-based ribavirin.

Viekira Pak™ (paritaprevir/ritonavir/ombitasvir daily plus dasabuvir 250 mg twice daily): duration, 12 weeks. Treatment duration is extended to 24 weeks as an alternative in those who have compensated cirrhosis and those who are PEG-IFN/ribavirin treatment experienced.

Olysio™ (simeprevir daily) plus Sovaldi™ (sofosbuvir daily): duration, 12 weeks. If compensated cirrhosis, treatment for 24 weeks with or without weight-based ribavirin.

Epclusa™ (sofosbuvir/velpatasvir daily): duration, 12 weeks.

Daklinza™ (daclatasvir daily) plus Sovaldi™ (sofosbuvir daily): duration, 12 weeks. If compensated cirrhosis, treatment for 24 weeks with or without weight-based ribavirin. Dose of daclatasvir may need to be adjusted if patient is on cytochrome P 450 3A/4 inducers or inhibitors.

► All drugs can be used in patients who have compensated cirrhosis, in patients who are PEG-IFN/ribavirin treatment experienced without cirrhosis, and in patients who are PEG-IFN/ribavirin treatment experienced with compensated cirrhosis.

Genotype 1 Treatment Options for Treatment-experienced Persons with Regimens Other Than PEG-IGN/Ribavirin

► With prior treatment with sofosbuvir plus ribavirin with or without PEG-IFN, recommended treatment:

Harvoni™ (ledipavir/sofosbuvir daily) with weight-based ribavirin: duration: no cirrhosis, 12 weeks; compensated cirrhosis, 12 weeks.        

► With prior treatment with NS3/4A protease inhibitor plus PEG/ribavirin, recommended treatment:

Harvoni™ (ledipavir/sofosbuvir daily) with weight-based ribavirin: duration: no cirrhosis, 12 weeks; compensated cirrhosis, 24 weeks. If ribavirin is used, duration is 24 weeks for compensated cirrhosis.

Epclusa™ (sofosbuvir/velpatasvir daily): duration: no cirrhosis, 12 weeks; compensated cirrhosis, 12 weeks.

Daklinza™ (daclatasvir daily) plus Sovaldi™ (sofosbuvir daily): duration: no cirrhosis, 12 weeks; compensated cirrhosis, 24 weeks (with or without weight-based ribavirin).              

Zepatier™ (elbasvir/grazoprevir daily) with weight-based ribavirin: duration: no cirrhosis, 12 weeks; compensated cirrhosis, 12 weeks. Extend treatment to 16 weeks in those who have genotype 1a if NS5A RAVs are present at baseline.

► Data on retreatment are limited for those with genotype 1 who are treatment experienced with simepravir plus sofosbuvir or NS5A inhibitors. If warranted, refer to a specialist for further management.

Next: Genotype 2, 3 Treatment Options

Genotype 2, 3 Treatment Options for Treatment-naive Persons Without Cirrhosis and for Those With Compensated Cirrhosis

Epclusa™ (sofosbuvir/velpatasvir daily): duration, 12 weeks. Addition of weight-based ribavirin is recommended for compensated cirrhotic patients who are PEG-IFN/ribavirin treatment experienced. A 12-week regimen with the addition of weight-based ribavirin can be used in sofosbuvir plus ribavirin treatment–experienced patients regardless of cirrhosis status.

Daklinza™ (daclatasvir daily) plus Sovaldi™ (sofosbuvir daily): duration, 12 weeks. For treatment-naïve patients, recommended treatment duration in compensated cirrhosis is 16 to 24 weeks for genotype 2 and 24 weeks for genotype 3. A 24-week regimen with the addition of weight-based ribavirin can be used in sofosbuvir plus ribavirin treatment-experienced patients regardless of cirrhosis status. Dose of daclatasvir may need to be adjusted if the patient is on cytochrome p450 3A/4 inducers or inhibitors. Referral to a specialist may be warranted.

► Both Epclusa™ and Daklinza™ plus Sovaldi™ can be used in patients who are PEG-IFN/ribavirin treatment experienced without cirrhosis and in patients who are PEG-IFN/ribavirin treatment experienced with compensated cirrhosis.

Treatment Options for Genotype 4 Treatment-naive Persons Without Cirrhosis or With Compensated Cirrhosis

Viekira Pak™ (paritaprevir/ritonavir/ombitasvir daily) and weight-based ribavirin: duration, 12 weeks.

Epclusa™ (sofosbuvir/velpatasvir daily): duration, 12 weeks.

Zepatier™ (elbasvir/grazoprevir daily): duration, 12 weeks. 12-week regimen if virologic relapse after prior PEG-IFN/ribavirin therapy; 16-week regimen with the addition of weight-based ribavirin if prior on-treatment virologic failure while on PEG-IFN/ribavirin.

Harvoni™ (ledipasvir/sofosbuvir daily): duration, 12 weeks. If compensated cirrhosis, add weight-based ribavirin; If compensated cirrhosis without addition of ribavirin, treat for 24 weeks.

► All drugs can be used in patients who are PEG-IFN/ribavirin treatment experienced without cirrhosis and in patients who are PEG-IFN/ribavirin treatment experienced with compensated cirrhosis.

Next: Treatment Options for Genotype 5, 6

Treatment Options for Genotype 5, 6 Treatment-naive Persons With and Without Cirrhosis

Epclusa™ (sofosbuvir/velpatasvir daily): duration, 12 weeks.  

Harvoni™ (ledipasvir/sofosbuvir daily): duration, 12 weeks.    

► Both Epclusa™ and Harvoni™ can be used in patients who are PEG-IFN/ribavirin treatment experienced without cirrhosis.

New Drugs in Development

Myriad research is ongoing in the field of HCV therapy, including new drug development. Thus, additional agents are expected to be approved in the near future.

 

Coming soon, the next part of this Special Report on Hepatitis C and Primary Care will focus on what happens if you don’t treat patients for HCV. Watch your email for eNewsletters from Patient Care and visit our homepage at www.patientcareonline.com to check for updates.

References:

American Association for the Study of Liver Diseases and Infectious Diseases Society of America.

Related Videos
Infectious disease specialist talks about COVID-19 vaccine development
COVID 19 impact on healthcare provider mental health
Physician mental health expert discusses impact of COVID-19 on health care workers
© 2024 MJH Life Sciences

All rights reserved.