This article is more than 5 years old. Information may no longer be current.
Triple-drug regimen led to high HCV cure rate
Click Here to Manage Email Alerts
The addition of a third direct-acting antiviral drug to a sofosbuvir plus ledipasvir regimen reduced the duration of treatment necessary for patients with chronic hepatitis C genotype 1 infection without cirrhosis to achieve sustained viral response, according to new research data.
“Treatment for HCV using all oral direct-acting antivirals (DAAs) for 8 to 24 weeks has been shown to result in high rates of eradication,” Shyam Kottilil, MD, PhD, professor of medicine in the division of infectious diseases, Institute of Human Virology at University of Maryland, told Healio Gastroenterology. “The minimum duration required to cure HCV has not been defined. The development of the simplest, short-duration regimen for HCV possible with high rates of cure is necessary for global eradication of the epidemic.”
Shyam Kottilil
Aiming to determine whether adding a third DAA to sofosbuvir/ledipasvir (Harvoni, Gilead) instead of ribavirin would reduce treatment duration, Kottilil and colleagues performed a single-center, open-label, phase 2a trial involving 60 patients with HCV genotype 1 infection enrolled at the Clinical Research Center of the NIH in 2013. Patients were sequentially assigned 12 weeks of sofosbuvir/ledipasvir, 6 weeks of sofosbuvir/ledipasvir plus GS-9669 (a non-nucleoside NS5B thumb site 3 inhibitor of HCV polymerase) or 6 weeks of sofosbuvir/ledipasvir plus GS-9451 (an inhibitor of the HCV NS3/4A protease).
SVR at 12 weeks after treatment completion was achieved by all 20 patients (100%; 95% CI, 83-100) who received 12 weeks of sofosbuvir/ledipasvir, by 19 of 20 patients (95%; 95% CI, 75-100) who received 6 weeks of sofosbuvir/ledipasvir plus G-9669 and by 19 of 20 patients (95%; 95% CI, 75-100) who received 6 weeks of sofosbuvir/ledipasvir plus GS-9451 (one patient was lost to follow-up after achieving SVR at 4 weeks). Most adverse events were mild, no patients discontinued treatment, and two unrelated severe adverse events occurred (pain after post-treatment liver biopsy and vertigo).
“This study demonstrates that combination therapy using multiple synergistic DAAs may allow for the further shortening of treatment duration for HCV,” Kottilil said. “Using the right combination of DAA therapy for as short as 6 weeks may result in high rates of SVR. Future studies with a large number of patients are required to confirm the findings of this preliminary study.”
Disclosure: The researchers report various financial and advisory ties with Abbott, Bristol-Meyers Squibb, Gilead, Merck and Vertex.
Click Here to Manage Email Alerts