Efficacy and safety results of patients with HCV genotype 2 or 3 infection treated with ombitasvir/paritaprevir/ritonavir and sofosbuvir with or without ribavirin (QUARTZ II‐III)

Abstract

The efficacy and safety of an investigational combination of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) plus sofosbuvir (SOF) ± ribavirin (RBV) in patients with HCV genotype 2 or 3 infection with or without cirrhosis was evaluated. Patients with HCV genotype 3 infection without cirrhosis were randomized to receive OBV/PTV/r + SOF ± RBV for 12 weeks; OBV/PTV/r + SOF + RBV was administered to genotype 3-infected patients with cirrhosis for 12 weeks and to genotype 2-infected patients without cirrhosis for either 6 or 8 weeks. Efficacy was assessed by sustained virologic response [HCV RNA <25 IU/mL] 12 weeks post-treatment (SVR12). Safety was assessed in all treated patients. In patients with genotype 3 infection with or without cirrhosis treated with 12 weeks of OBV/PTV/r + SOF ± RBV, the overall SVR12 rate was 98% (50/51), with no virologic failures. Patients with genotype 2 infection treated with OBV/PTV/r + SOF + RBV had SVR12 rates of 90% (9/10) and 44% (4/9) following 8- and 6-week treatment durations, respectively; failure to achieve SVR12 for these patients was due to relapse without baseline or treatment-emergent resistance-associated substitutions. Thus, the investigational combination of OBV/PTV/r with SOF ± RBV was well tolerated and achieved high SVR rates with no virologic failures in patients with genotype 3 infection. Combining direct-acting antivirals with complementary mechanisms of action and different viral targets may be an effective treatment strategy that may allow for shorter durations of therapy.

Current Status of Direct Acting Antiviral Agents against Hepatitis C Virus Infection in Pakistan

“…Ombitasvir with paritaprevir and ritonavir (NS5A, NS3/NS4A inhibitor and HIV antiretroviral drug): approved for genotype 1 and 4 patients coinfected with HIV [ 53 , 54 ];…”

Hepatitis C virus genotype 3: clinical features, current and emerging viral inhibitors, future challenges

“…As a pharmaco-enhancer, ritonavir has no activity against HCV; instead, it inhibits the metabolism of paritaprevir, thereby increasing peak and trough drug exposures and allowing for a once-daily dose of ABT-450 [ 97 ]. The NAVIGATOR trial combined ABT-450/r with ombitasvir (ABT-267), an NS5A inhibitor, for 12 weeks in genotype 3 treatment-naïve non-cirrhotic patients, achieving SVR rates of 50% without RBV and just 9% with RBV [ 98 ]. Though the medication was well tolerated, the low SVRs prompted discontinuation of the trial.…”

“…Though the medication was well tolerated, the low SVRs prompted discontinuation of the trial. Similarly, in patients with or without cirrhosis, the QUARTZ II-III trial combinations of ombitasvir/paritaprevir/ritonavir plus sofosbuvir with or without RBV showed an overall SVR of 98% after 12 weeks [ 98 ]. The study noted that combining DAAs with complementary mechanisms of action and virological targets may be an effective therapeutic strategy.…”

Treatment of Genotype 3 Chronic Hepatitis C Virus Infection

“…All six noncirrhotic treatment-naïve patients who were treated with this combination for 12 weeks as part of the QUARTZ-II study achieved SVR. 25…”

“…All six noncirrhotic treatment-naïve patients who were treated with this combination for 12 weeks as part of the QUARTZ-II study achieved SVR. 25 The C-CREST study assessed the efficacy of an eight-week combination of grazoprevir, with MK-3682, an NS5B inhibitor, and one of two NS5A inhibitors, either elbasvir or MK-8408, in treatment-naïve noncirrhotic patients with GT3 HCV. The SVR rates in the four treatment arms were: 90% (19/21) with grazoprevir, elbasvir, and MK-3682 (300 mg); 86% (19/22) with grazoprevir, elbasvir, and MK-3682 (450 mg); 95% (20/21) with grazoprevir, MK-8408, and MK-3682 (300 mg); and 91% (20/22) with grazoprevir, MK-8408, and MK-3682 (450 mg).…”