Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial

Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse with 17 confirmed and 4 provisional subtypes. In this report, HCV GT4-infected patient samples from Phase 2/3 clinical studies were analysed to characterize global demographics and genetic diversity of GT4 infection among patients treated with ombitasvir (OBV, NS5A inhibitor) plus paritaprevir/r (NS3/4A inhibitor codosed with ritonavir). Among 17 subtypes isolated from GT4-infected patients in the PEARL-I and AGATE-I studies, subtype prevalence by country of enrolment and country of origin suggested that subtypes 4a and 4d were likely circulating in Europe, while heterogeneous GT4 subtypes and a portion of GT4a detected in European and North American countries were likely due to immigration of HCV-infected patients from Africa. The distributions of birth cohort and race were also significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. In addition, phylogenetic analyses of NS5A sequences revealed clustering within subtype 4a which segregated by the patient-reported country of origin and the presence of the L30R/S polymorphism. HCV NS5A sequences derived from GT4a-infected patients who originated from Europe and the United States clustered separately from sequences derived from patients who originated from Egypt, suggesting that genetically distinct strains of subtype 4a may be circulating globally. Finally, NS5A baseline polymorphisms were frequently detected at amino acid positions of interest for the inhibitor-class and OBV retained activity against 37 of 39 NS5A GT4 clinical isolates, with no impact on treatment outcome in the PEARL-I and AGATE-I studies.

Section: Discussionmentioning

confidence: 99%

Section: Examining the Epidemiological Profile Of Gt4 Infection In Frmentioning

confidence: 99%

Characterization of demographics and NS5A genetic diversity for hepatitis C virus genotype 4‐infected patients with or without cirrhosis treated with ombitasvir/paritaprevir/ritonavir

Schnell

Tripathi

Beyer

et al. 2018

“…Phase 3b clinical study demonstrated 100% SVR12 for patients with GT1b and compensated cirrhosis after treatment with OBV/PTV/r+DSV without RBV, resulting in label and treatment guidelines updates for this population . Patients with GT4 infection are recommended treatment with the 2‐DAA combination of OBV/PTV/r+RBV, which also resulted in high SVR rates in clinical trials …”

Section: Introductionmentioning

confidence: 99%

Real‐world effectiveness of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in patients with hepatitis C virus genotype 1 or 4 infection: A meta‐analysis

Wedemeyer

Craxı̀

Zuckerman

et al. 2017

“…AGATE‐II is a phase‐III trial carried out in Egypt, evaluating OBV plus PTV/r with RBV for GT4‐infected patients, including those with compensated cirrhosis . In total, 160 patients were enrolled, 100 noncirrhotic and 60 compensated cirrhotic patients.…”

Section: Interferon‐free Therapiesmentioning

confidence: 99%

Hepatitis C virus genotype 4: Genotype 1's little brother

Llaneras

Riveiro‐Barciela

Buti

et al. 2016

Treatment for hepatitis C virus genotype 4 infection has undergone a major advance over the past 5 years with the emergence of direct-acting antiviral agents. Previously, genotype 4 treatment had been limited to the combination of pegylated interferon and ribavirin, with low rates of sustained virological response. The combinations of new direct-acting agents have resulted in a radical improvement in hepatitis C therapy. Much of the currently available efficacy and safety information in the treatment of genotype 4 has been extrapolated through the results of genotype 1. In this report, we review the efficacy and safety data obtained in recent studies focusing on genotype 4 patients, including special populations, such as those with decompensated cirrhosis.