Back HCV Treatment Approved HCV Drugs Response-Guided DAA Triple Regimen May Cure Hepatitis C in as Little as 3 Weeks

Response-Guided DAA Triple Regimen May Cure Hepatitis C in as Little as 3 Weeks


Response-guided therapy using 3 direct-acting antivirals without ribavirin cured a majority of easier-to-treat genotype 1b hepatitis C patients in just 3 weeks, according to results from a small pilot study published in the October 2016 edition of The Lancet Gastroenterology & Hepatology.

Direct-acting antiviral agents (DAAs) used in interferon-free regimens have revolutionized treatment for chronic hepatitis C, but researchers continue to explore shorter courses of therapy that would be less expensive, more convenient, and might encourage better adherence.

Approved DAA regimens are usually taken for 8 or 12 weeks. A few studies have looked at multidrug regimens taken for 6 weeks or less. Combining multiple drugs that target different steps of the hepatitis C virus (HCV) lifecycle improve the chances of successful treatment with shorter regimens. Shortening treatment too much, however, could raise the risk of treatment failure and drug resistance, especially for difficult-to-treat patients such as those with prior treatment failure, HCV genotype 3, high baseline viral load, or liver cirrhosis.

George Lau from Humanity and Heath Medical Centre in Hong Kong and colleagues evaluated a 3-drug DAA regimen using response-guided therapy to see if patients who responded rapidly at the beginning of treatment could be cured in just 3 weeks. Rapid virological response (usually measured at week 4) was used in the interferon era to predict which patients were unlikely to be cured and therefore could be taken off poorly tolerated therapy. This study tested whether "ultrarapid" virological response could be used to determine which patients could be cured with a vey short course of treatment.

This open-label Phase 2a study (NCT02470858) included 26 Chinese patients with HCV subtype 1b, which is easier to treat than subtype 1a. Just over half had previously been treated for hepatitis C. Most had absent or mild liver fibrosis (stage F0-F1) and none had cirrhosis. About two-thirds had the favorable IL28B "CC" gene pattern associated with good interferon response. At baseline the mean HCV viral load was approximately 6.5 log IU/mL.

Participants were randomly assigned to receive 3-drug multiclass regimens consisting of the HCV NS5B polymerase inhibitor sofosbuvir (Sovaldi), one of the NS5A inhibitors ledipasvir (coformulated with sofosbuvir in Harvoni) or daclatasvir (Daklinza), and one of the NS3/4A protease inhibitors asunaprevir (Sunvepra) or simeprevir (Olysio). Group 1 received sofosbuvir/ledipasvir and asunaprevir (n=12); Group 2 received sofosbuvir, daclatasvir, and simeprevir (n=6); and Group 3 received sofosbuvir, daclatasvir, and asunaprevir (n=8).

Participants with ultrarapid virological response -- defined as HCV RNA <500 IU/mL by day 2 of therapy -- stopped treatment after 3 weeks, while the rest switched to a dual regimen of sofosbuvir and ledipasvir and were treated for 8 to 12 weeks.

The primary endpoint was sustained virological response, or continued undetectable HCV viral load at 12 weeks post-treatment (SVR12). Results were previously presented in part at the 2015 AASLD Liver Meeting.


  • 18 participants (69%) -- 6 in each treatment group -- achieved ultrarapid virological response at day 2 of therapy.
  • All patients with ultrarapid virological response who were treated with triple therapy for 3 weeks achieved SVR12.
  • People who achieved ultrarapid virological response had lower baseline viral load on average and were less likely to have high baseline viral load.
  • Treatment was generally safe and well-tolerated, with no serious adverse events.
  • The most common adverse events were fatigue and headache.

"In this proof-of-concept study, all patients with chronic HCV without cirrhosis who achieved an ultrarapid virological response on triple direct-acting antiviral regimens by day 2 and received 3 weeks of treatment were cured, with excellent tolerability," the study authors concluded.

By shortening the duration of therapy from the currently recommended 12 weeks to 3 weeks, they added, "we could drastically reduce the cost of therapy and the rate of adverse events."

These results suggest that shortening therapy to 3 weeks may be adequate for some easy-to-treat patients and that early response can help determine who should continue therapy for the usual 8- or 12-week course. People with HCV subtype 1b may be the best candidates for shortened therapy.

The researchers recommended that further large-scale studies should be done to confirm their findings.



G Lau, Y Benhamou, G Chen, et al. Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study. The Lancet Gastroenterology & Hepatology1(2):97-104. October 2016.