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, Roger Trinh, Mark Sulkowski, 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, Roger Trinh, Mark Sulkowski

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.

Figures

Figure 1.
Figure 1.
Trial profile. Patient disposition from screening through study completion is shown. Abbreviations: G/P, glecaprevir/pibrentasvir; ITT, intent-to-treat (includes all patients who received at least 1 dose of the study drug); mITT, modified intent-to-treat (excludes nonvirologic failures.)
Figure 2.
Figure 2.
Efficacy of glecaprevir/pibrentasvir. Rates of sustained virologic response 12 weeks after treatment (SVR12) are shown in the intent-to-treat (white) and modified intent-to-treat (gray) populations. Dotted line represents the noninferiority threshold applied to the primary endpoint (SVR12) analysis. Reasons for nonresponse are tabled. Abbreviations: ITT, intent-to-treat (includes all patients who received at least 1 dose of the study drug); mITT, modified intent-to-treat (excludes nonvirologic failures); SVR12, sustained virologic response 12 weeks after treatment.

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