NCCC Clinical Pearls: HCV Treatment Interruption

Case Summary

A 67-year-old cisgender male with chronic HCV mono-infection was seen for treatment evaluation.  He had no history of prior HCV treatment, and initial assessment revealed genotype 1a and a fibrosis score of F3/F4.  Direct-acting antiviral (DAA) therapy using 12-weeks of sofosbuvir/velpatasvir (SOF/VEL) was initiated.  The patient missed their early follow-up appointment, however a few months later he called the clinic requesting an urgent appointment.  He was being released from the hospital, where he’d been for the last 3 weeks.  Although he had missed no doses of SOF/VEL prior to the hospitalization, he had not been able to continue HCV therapy during the admission.  After reviewing medication pick-up date and subsequent adherence with the patient, the clinician determined that the patient had received 9 weeks of SOF/VEL and missed exactly 21 days of medication.  

The caller is asking how to proceed from this point on.  Should they finish the missed doses or extend therapy?

NCCC Consultant Response:

Questions such as these around treatment interruptions are received frequently by the NCCC’s HCV Warmline (  Prior to October 2021, there were no specific recommendations in the American Association for the Study of Liver Diseases (AASLD) HCV treatment guidelines on how to manage such interruptions1.  The updated guidelines now have a dedicated section on incomplete adherence, with a corresponding table2. Recommendations for people with HIV-HCV co-infection do not differ from recommendations for people with HCV mono-infection.

This case highlights the nuances of treatment in real-life settings: because this person had missed 21 days of therapy, AASLD guidelines would recommend stopping treatment and assessing for sustained virologic response at 12 weeks (SVR12) after the end of treatment. However, for people who have missed 8-20 consecutive days after receiving more than 28 days of initial treatment, guidelines recommend restarting DAA therapy as soon as possible while simultaneously obtaining an HCV RNA.  If the HCV RNA comes back undetectable, current guidelines recommend finishing out the remaining course – with a caveat to extend therapy by 4 weeks for people with genotype 3 or cirrhosis.  If the HCV RNA is >25 IU/L, guidelines recommend stopping therapy and retreating according to the retreatment recommendations.

For this person, who has missed exactly 21 consecutive days of therapy, following the guidelines would mean stopping treatment, waiting several more weeks to assess for SVR12, and then retreating (if needed) per the retreatment recommendations.  However, there is currently little clinical data to inform this decision.  To our knowledge, 3 studies have evaluated outcomes for patients with incomplete adherence3,4,5. The ANCHOR study5 followed 100 individuals with ongoing opioid use disorder and chronic HCV who were treated with SOF/VEL, and found a high rate of SVR12 (82%) despite missed doses being fairly common.  SIMPLIFY3 looked at 103 individuals with recent (within the previous 6 months) injection drug use and monitored patient adherence via electronic blister pack. Despite the fact that 32% of participants were considered “non-adherent” (defined as taking <90% of doses), treatment completion and virologic response rates were still high, with 96% completing therapy and 94% achieving SVR12.  Finally, a study by Fabbiani et al4 retrospectively analyzed 365 individuals who prematurely stopped HCV treatment and stratified them according to fibrosis stage (F0-F3 vs. cirrhosis). In people with lower stage disease, 99.1% (109/110) achieved SVR12 if they received at least 4 weeks of therapy.  In people with cirrhosis, however, lower SVR12 rates were observed if someone was treated for < 8 weeks: 83.3% (n = 25/30) vs. 94.6% (n = 209/221) if treated for ≥ 8 weeks (p = 0.038).

These studies highlight real-life experience with treatment interruptions and offer reassurance that the majority of treated people will still clear despite imperfect adherence. There is a lack of clear data to guide exactly how many missed doses should warrant stopping therapy, or if DAAs can be reused after a previous incomplete course. Additionally, there is no standard definition for “treatment-experienced,” and expert opinion varies on how many doses of DAA treatment categorizes someone as treatment-experienced.

The HCV Warmline offers support to help review such “real-life” nuances and can be used as a clinical resource for these tough cases.  For the case above, we made recommendations per the guidelines and also endorsed the option of resuming therapy as soon as possible to finish the remaining 3 weeks of therapy.  We reviewed the option to extend for an additional 4 weeks as the patient was initially staged as F3/F4 and could be considered as having compensated cirrhosis.  We advised the caller to work with the patient to identify opportunities to support adherence as much as possible for the remainder of therapy.

Providers with questions about hepatitis C management are welcome to discuss these with the NCCC's multi-professional consultant team by calling the HCV Warmline at (844) HEP‐INFO or (844) 437-4636 Monday – Friday, 9 a.m. – 8 p.m. ET.  Questions and cases may also be submitted online through the portal:


  1. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C.
  2. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Monitoring Patients Who Are Starting HCV Treatment, Are on Treatment, or Have Completed Therapy. Figure 1: Recommended Management of DAA Treatment Interruptions of Treatment-Naive Patients, Without Cirrhosis or With Compensated Cirrhosis, Receiving Glecaprevir/Pibrentasvir or Sofosbuvir/Velpatasvir.
  3. Cunningham EB, Amin J, Feld JJ, et al. Adherence to sofosbuvir and velpatasvir among people with chronic HCV infection and recent injection drug use: the SIMPLIFY study. Int J Drug Policy. 2018; 62:14-23.
  4. Fabbiani M, Lombardi A, Colaneri M, et al. High rates of sustained virological response despite premature discontinuation of directly acting antivirals in HCV-infected patients treated in a real-life setting. J Viral Hepat. 2021;28(3):558-568.
  5. Rosenthal ES, Nussdorf L, D’Amore A, et al. 2900. High Rates of Experienced and Witnessed Opioid Overdose in PWID Receiving HCV Treatment: Data from the ANCHOR Study. Open Forum Infect Dis. 2019 Oct 23;6(Suppl 2): S83. doi: 10.1093/ofid/ofz359.178. PMCID: PMC6808729.

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