Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1

The EXPEDITION-2 Study

Jürgen K. Rockstroh, Karine Lacombe, Rolando M. Viani, Chloe Orkin, David Wyles, Anne F. Luetkemeyer, Ruth Soto-Malave, Robert Flisiak, Sanjay Bhagani, Kenneth E. Sherman, Tatiana Shimonova, Peter Ruane, Joseph Sasadeusz, Jihad Slim, Zhenzhen Zhang, Suvajit Samanta, Teresa I. Ng, Abhishek Gulati, Matthew P. Kosloski, Nancy S. Shulman & 2 others Roger Trinh, Mark Sulkowski

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1010-1017
Number of pages8
JournalClinical Infectious Diseases
Volume67
Issue number7
DOIs
StatePublished - Sep 14 2018

Fingerprint

Hepacivirus
HIV-1
Safety
Genotype
Fibrosis
Therapeutics
Coinfection
Interferons
Ribavirin
Chronic Hepatitis C
Treatment Failure
Clinical Trials
Confidence Intervals

Keywords

  • cirrhosis
  • direct-acting antiviral
  • EXPEDITION-2
  • hepatitis C
  • HIV coinfection

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1 : The EXPEDITION-2 Study. / Rockstroh, Jürgen K.; Lacombe, Karine; Viani, Rolando M.; Orkin, Chloe; Wyles, David; Luetkemeyer, Anne F.; Soto-Malave, Ruth; Flisiak, Robert; Bhagani, Sanjay; Sherman, Kenneth E.; Shimonova, Tatiana; Ruane, Peter; Sasadeusz, Joseph; Slim, Jihad; Zhang, Zhenzhen; Samanta, Suvajit; Ng, Teresa I.; Gulati, Abhishek; Kosloski, Matthew P.; Shulman, Nancy S.; Trinh, Roger; Sulkowski, Mark.

In: Clinical Infectious Diseases, Vol. 67, No. 7, 14.09.2018, p. 1010-1017.

Research output: Contribution to journalArticle

Rockstroh, JK, Lacombe, K, Viani, RM, Orkin, C, Wyles, D, Luetkemeyer, AF, Soto-Malave, R, Flisiak, R, Bhagani, S, Sherman, KE, Shimonova, T, Ruane, P, Sasadeusz, J, Slim, J, Zhang, Z, Samanta, S, Ng, TI, Gulati, A, Kosloski, MP, Shulman, NS, Trinh, R & Sulkowski, M 2018, 'Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1: The EXPEDITION-2 Study', Clinical Infectious Diseases, vol. 67, no. 7, pp. 1010-1017. https://doi.org/10.1093/cid/ciy220
Rockstroh, Jürgen K. ; Lacombe, Karine ; Viani, Rolando M. ; Orkin, Chloe ; Wyles, David ; Luetkemeyer, Anne F. ; Soto-Malave, Ruth ; Flisiak, Robert ; Bhagani, Sanjay ; Sherman, Kenneth E. ; Shimonova, Tatiana ; Ruane, Peter ; Sasadeusz, Joseph ; Slim, Jihad ; Zhang, Zhenzhen ; Samanta, Suvajit ; Ng, Teresa I. ; Gulati, Abhishek ; Kosloski, Matthew P. ; Shulman, Nancy S. ; Trinh, Roger ; Sulkowski, Mark. / Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1 : The EXPEDITION-2 Study. In: Clinical Infectious Diseases. 2018 ; Vol. 67, No. 7. pp. 1010-1017.
@article{e676ce1b1ed8454887d81900aafcfe29,
title = "Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1: The EXPEDITION-2 Study",
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.",
keywords = "cirrhosis, direct-acting antiviral, EXPEDITION-2, hepatitis C, HIV coinfection",
author = "Rockstroh, {J{\"u}rgen K.} and Karine Lacombe and Viani, {Rolando M.} and Chloe Orkin and David Wyles and Luetkemeyer, {Anne F.} and Ruth Soto-Malave and Robert Flisiak and Sanjay Bhagani and Sherman, {Kenneth E.} and Tatiana Shimonova and Peter Ruane and Joseph Sasadeusz and Jihad Slim and Zhenzhen Zhang and Suvajit Samanta and Ng, {Teresa I.} and Abhishek Gulati and Kosloski, {Matthew P.} and Shulman, {Nancy S.} and Roger Trinh and Mark Sulkowski",
year = "2018",
month = "9",
day = "14",
doi = "10.1093/cid/ciy220",
language = "English (US)",
volume = "67",
pages = "1010--1017",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "7",

}

TY - JOUR

T1 - Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1

T2 - The EXPEDITION-2 Study

AU - Rockstroh, Jürgen K.

AU - Lacombe, Karine

AU - Viani, Rolando M.

AU - Orkin, Chloe

AU - Wyles, David

AU - Luetkemeyer, Anne F.

AU - Soto-Malave, Ruth

AU - Flisiak, Robert

AU - Bhagani, Sanjay

AU - Sherman, Kenneth E.

AU - Shimonova, Tatiana

AU - Ruane, Peter

AU - Sasadeusz, Joseph

AU - Slim, Jihad

AU - Zhang, Zhenzhen

AU - Samanta, Suvajit

AU - Ng, Teresa I.

AU - Gulati, Abhishek

AU - Kosloski, Matthew P.

AU - Shulman, Nancy S.

AU - Trinh, Roger

AU - Sulkowski, Mark

PY - 2018/9/14

Y1 - 2018/9/14

N2 - 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.

AB - 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.

KW - cirrhosis

KW - direct-acting antiviral

KW - EXPEDITION-2

KW - hepatitis C

KW - HIV coinfection

UR - http://www.scopus.com/inward/record.url?scp=85049582109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049582109&partnerID=8YFLogxK

U2 - 10.1093/cid/ciy220

DO - 10.1093/cid/ciy220

M3 - Article

VL - 67

SP - 1010

EP - 1017

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 7

ER -