Does discontinuing Mavyret (glecaprevir/pibrentasvir) after three days increase the risk of developing resistance?

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Last updated: April 23, 2025View editorial policy

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From the Guidelines

Stopping Mavyret (glecaprevir/pibrentasvir) after only three days of treatment significantly increases the risk of developing viral resistance, and thus, it is crucial to complete the full prescribed course of 8-16 weeks to achieve sustained virologic response (cure) and minimize the risk of resistance development. The recommended treatment duration for Mavyret depends on the specific hepatitis C virus (HCV) genotype, liver condition, and treatment history 1. Prematurely discontinuing the medication allows the virus to develop mutations that can make it resistant not only to Mavyret but potentially to other direct-acting antivirals as well. This resistance occurs because some viral particles naturally have slight genetic variations, and when treatment pressure is applied but not maintained long enough to eliminate all virus, these resistant variants can multiply and become the dominant strain.

According to the EASL recommendations on treatment of hepatitis C, the fixed-dose combination of glecaprevir and pibrentasvir is recommended for 8 weeks in treatment-naïve and treatment-experienced patients infected with HCV genotypes 1a, 1b, 2,4,5 or 6 without cirrhosis 1. However, in patients with compensated (Child-Pugh A) cirrhosis, the treatment duration may need to be extended to 12 weeks. The presence of resistance-associated substitutions (RASs) in the NS5A region may also impact the treatment outcome, and thus, resistance testing may be necessary in certain cases 1.

If you've stopped Mavyret after three days, you should contact your healthcare provider immediately to discuss restarting treatment. Restarting treatment promptly may prevent resistance development, but your provider may need to check for resistance before determining the best approach forward. The EASL recommendations suggest that in settings where sequence analysis of the NS5A region is available and affordable, patients infected with certain subtypes and those with RASs known to confer resistance to NS5A inhibitors should be considered for alternative treatment regimens 1.

In summary, completing the full prescribed course of Mavyret is essential to achieve sustained virologic response and minimize the risk of resistance development. If treatment is stopped prematurely, it is crucial to consult with a healthcare provider to determine the best course of action. The EASL recommendations provide guidance on treatment duration and resistance testing, and healthcare providers should consider these guidelines when making treatment decisions 1.

From the Research

Mavyret Treatment and Resistance

  • The provided studies do not directly address the issue of Mavyret treatment for only three days and its potential to lead to resistance 2, 3, 4, 5, 6.
  • However, it is known that direct-acting antiviral (DAA) therapies, including Mavyret (glecaprevir/pibrentasvir), have a high barrier to resistance 3.
  • The studies suggest that glecaprevir/pibrentasvir is highly effective in treating chronic hepatitis C virus infection in adults, with high cure rates in all six HCV genotypes 3, 6.
  • Treatment failure and the emergence of viral resistance can occur, particularly in patients with prior DAA treatment failures 2, 5.
  • The development of resistance-associated variants (RAVs) can affect the efficacy of subsequent treatments, highlighting the importance of careful patient management and treatment selection 5.

Key Findings

  • Glecaprevir/pibrentasvir has been shown to be effective in treating patients with HCV genotype 1 or 3 infection, with sustained virologic response rates of 99.1% and 95%, respectively 3.
  • The treatment is well tolerated, with common adverse events including headache and fatigue 6.
  • Patients with prior DAA treatment failures can achieve high SVR rates with glecaprevir/pibrentasvir treatment, although some may have low susceptibility to the treatment due to the presence of certain RAVs 5.

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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