6-week Hepatitis C DAA drug regimen is effective
Posted on April 14, 2015
A simple 6-week course of three direct-acting antiviral drugs appears to be effective and well tolerated in patients with chronic HCV genotype 1 infection without cirrhosis
Simple hepatitis C treatment regimens with a short duration, low pill burdens, and few adverse effects could improve patient adherence, which is vital considering that the ultimate goal is to achieve global elimination of hepatitis C. Anita Kohli and colleagues conducted a single-center, proof-of-concept phase 2A cohort study, recently published in the journal Lancet, to explore whether the addition of a third direct acting antiviral (DAA) drug instead of ribavirin to sofosbuvir and ledipasvir would result in a shorter, more efficacious, treatment regimen (Kohli A et al. Lancet. 2015 Mar 21;385(9973):1107-1113).
This clinical trial article is available for free for a limited time in the specialist section of the American Journal of Medicine Hepatitis C Resource Center. Click here!
The authors concluded that patients with chronic HCV genotype 1 infection without cirrhosis could indeed be successfully treated with a 6-week course of three oral DAA drugs with different mechanisms of action. For this study, 60 adult patients were sequentially enrolled into three groups, each with a different DAA treatment regimen:
- Group 1: 12 weeks of sofosbuvir (400 mg) and ledipasvir (90 mg) given as a combination tablet taken once a day. All 20 patients had unquantifiable HCV RNA 12 weeks after completion of treatment—ie, achieved SVR12. 17 participants had an unquantifiable level of HCV RNA by week 4 of treatment.
- Group 2: 6 weeks of sofosbuvir (400 mg) and ledipasvir (90 mg) given as a combination tablet taken once a day, and GS-9669 (500 mg: a non-nucleoside NS5B thumb site 3 inhibitor of HCV polymerase) given as two 250 mg tablets once a day. 19 of 20 patients achieved SVR12. One patient relapsed 2 weeks after completion of treatment. This patient had advanced stage 3 liver disease and a high baseline HCV viral load, both of which are predictors of poor response to some therapeutic regimens that contain only DAA drugs.
- Group 3: 6 weeks of sofosbuvir (400 mg) and ledipasvir (90 mg) given as a combination tablet taken once a day, and GS-9451 (80 mg: an inhibitor of the HCV NS3/4A protease) given as one tablet once a day. 19 of 20 patients achieved SVR12. One patient was incarcerated into prison after having SVR after their 4-week follow up visit after completion of therapy, and data obtained after incarceration could not be included for publication.
- All participants treated with the combination of sofosbuvir, ledipasvir and GS-9669, or that of sofosbuvir, ledipasvir, and GS-9451, had an unquantifiable concentration of HCV RNA by week 4 of treatment
- Baseline characteristics were similar between all treatment groups: participants were mainly black (53, 88%), men (43, 72%), had IL28 non-CC genotype (48, 80%), were infected with HCV genotype 1a (42, 70%), and had high baseline concentrations of plasma HCV RNA (>800 000 IU/mL; 42, 70%).
- All 60 patients completed treatment. The most common adverse events were diarrhea, headache, and fatigue, and most adverse events were mild.
All 3 regimens were well tolerated, rapidly suppressed HCV viremia in patients, and resulted in high rates of SVR12. The authors noted that viral kinetic modelling suggests that the three-drug regimen of sofosbuvir, ledipasvir, and GS-9451—targeting three different stages of the HCV lifecycle—resulted in enhanced HCV clearance compared with other regimens that target only two stages. The authors concluded that: “In view of the confines of the population studied, we can now speculate that a 6 week course of three direct-acting antiviral drugs can result in SVR12 in at least 75%, and perhaps nearly 100%, of people infected with HCV. This quick and simple treatment for HCV might prove relevant for the global elimination of hepatitis C, in which simple and well tolerated therapy of short duration is needed to ensure adherence.”