학술논문
Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Coinfected With Hepatitis C Virus and Human Immunodeficiency Virus Type 1: The EXPEDITION-2 Study.
Document Type
Academic Journal
Author
Rockstroh JK; Department of Medicine, Universitätsklinikum Bonn, Germany.; Lacombe K; Infectious Diseases Unit, Inserm UMR-S1136, Université Pierre et Marie Curie, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, Paris, France.; Viani RM; Infectious Disease Development, AbbVie Inc, Chicago, Illinois.; Orkin C; Infection and immunology Barts Health, Royal London Hospital, United Kingdom.; Wyles D; Division of Infectious Diseases, Denver Health Medical Center, Colorado.; Luetkemeyer AF; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General, University of California.; Soto-Malave R; Innovative Care P.S.C., Bayamon, Puerto Rico.; Flisiak R; Department of Infectious Diseases and Hepatology, Klinika Chorób Zakaznych i Hepatologii UM w Bialymstoku, Bialystok, Poland.; Bhagani S; Department of Infectious Diseases/HIV Medicine, Royal Free London Foundation Trust, United Kingdom.; Sherman KE; Division of Digestive Diseases, University of Cincinnati, Ohio.; Shimonova T; State Budgetary Healthcare Institution of Moscow, Infectious Clinical Hospital #2 of Moscow City Healthcare Department, Russia.; Ruane P; Ruane Medical & Liver Health Institute, Los Angeles, California.; Sasadeusz J; Victorian Infectious Disease Service, Royal Melbourne Hospital, Parkville, Victoria, Australia.; Slim J; Infectious Disease Division, Department of Internal Medicine, St. Michael's Medical Center, Newark, New Jersey.; Zhang Z; Data and Statistical Sciences, AbbVie Inc, Chicago, Illinois.; Samanta S; Data and Statistical Sciences, AbbVie Inc, Chicago, Illinois.; Ng TI; HCV Clinical Virology, AbbVie Inc, Chicago, Illinois.; Gulati A; Clinical Pharmacology and Pharmacometrics, AbbVie Inc, Chicago, Illinois.; Kosloski MP; Clinical Pharmacology and Pharmacometrics, AbbVie Inc, Chicago, Illinois.; Shulman NS; Infectious Disease Development, AbbVie Inc, Chicago, Illinois.; Trinh R; Infectious Disease Development, AbbVie Inc, Chicago, Illinois.; Sulkowski M; Divisions of Infectious Diseases and Gastroenterology/Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 9203213 Publication Model: Print Cited Medium: Internet ISSN: 1537-6591 (Electronic) Linking ISSN: 10584838 NLM ISO Abbreviation: Clin Infect Dis Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Once-daily glecaprevir coformulated with pibrentasvir (glecaprevir/pibrentasvir) demonstrated high rates of sustained virologic response 12 weeks after treatment (SVR12) in patients with hepatitis C virus (HCV) genotype 1-6 infection. This phase 3 study evaluated the efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV genotype 1-6 and human immunodeficiency virus type 1 (HIV-1) coinfection, including patients with compensated cirrhosis.
Methods: EXPEDITION-2 was a phase 3, multicenter, open-label study evaluating glecaprevir/pibrentasvir (300 mg/120 mg) in HCV genotype 1-6/HIV-1-coinfected adults without and with compensated cirrhosis for 8 and 12 weeks, respectively. Patients were either HCV treatment-naive or experienced with sofosbuvir, ribavirin, or interferon, and antiretroviral therapy (ART) naive or on a stable ART regimen. Treatment-experienced genotype 3-infected patients were excluded. The primary endpoint was the SVR12 rate.
Results: In total, 153 patients were enrolled, including 16 (10%) with cirrhosis. The SVR12 rate was 98% (n = 150/153; 95% confidence interval, 95.8-100), with no virologic failures in 137 patients treated for 8 weeks. One genotype 3-infected patient with cirrhosis had on-treatment virologic failure. Most adverse events were mild in severity; 4 patients (2.6%) had serious adverse events, all deemed unrelated to glecaprevir/pibrentasvir. Treatment discontinuation was rare (<1%). All patients treated with ART maintained HIV-1 suppression (<200 copies/mL) during treatment.
Conclusions: Glecaprevir/pibrentasvir for 8 weeks in noncirrhotic and 12 weeks in cirrhotic patients is a highly efficacious and well-tolerated treatment for HCV/HIV-1 coinfection, regardless of baseline HCV load or prior treatment with interferon or sofosbuvir.
Clinical Trial Registration: NCT02738138.
Methods: EXPEDITION-2 was a phase 3, multicenter, open-label study evaluating glecaprevir/pibrentasvir (300 mg/120 mg) in HCV genotype 1-6/HIV-1-coinfected adults without and with compensated cirrhosis for 8 and 12 weeks, respectively. Patients were either HCV treatment-naive or experienced with sofosbuvir, ribavirin, or interferon, and antiretroviral therapy (ART) naive or on a stable ART regimen. Treatment-experienced genotype 3-infected patients were excluded. The primary endpoint was the SVR12 rate.
Results: In total, 153 patients were enrolled, including 16 (10%) with cirrhosis. The SVR12 rate was 98% (n = 150/153; 95% confidence interval, 95.8-100), with no virologic failures in 137 patients treated for 8 weeks. One genotype 3-infected patient with cirrhosis had on-treatment virologic failure. Most adverse events were mild in severity; 4 patients (2.6%) had serious adverse events, all deemed unrelated to glecaprevir/pibrentasvir. Treatment discontinuation was rare (<1%). All patients treated with ART maintained HIV-1 suppression (<200 copies/mL) during treatment.
Conclusions: Glecaprevir/pibrentasvir for 8 weeks in noncirrhotic and 12 weeks in cirrhotic patients is a highly efficacious and well-tolerated treatment for HCV/HIV-1 coinfection, regardless of baseline HCV load or prior treatment with interferon or sofosbuvir.
Clinical Trial Registration: NCT02738138.