ArticlesEfficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial
Introduction
HIV co-infection is common in patients with hepatitis C virus (HCV) infection.1, 2, 3, 4 HIV co-infection accelerates the progression of HCV-related liver disease, making HCV a leading cause of morbidity and mortality in patients with HIV-1.5, 6, 7 Compared with patients with HCV monoinfection, patients with HIV and HCV co-infection have higher baseline HCV viral loads, more rapid progression of liver disease,8 and an increased risk of cirrhosis, end-stage liver disease, and hepatocellular carcinoma.9 Co-infected patients are also more susceptible to anaemia and more rapid progression to AIDS and AIDS-related death.5, 6, 10 Direct-acting antiviral agents have revolutionised treatment of HCV infection;11, 12, 13, 14, 15 however, many regimens for patients with HIV and HCV co-infection are restricted by their requirement for co-administration with peginterferon or ribavirin, particularly in patients infected with HCV genotype 1a and in those with cirrhosis.16 Grazoprevir, an NS3/4A protease inhibitor (MK-5172), and elbasvir, an NS5A inhibitor (MK-8742; Merck & Co, Inc, Kenilworth, NJ, USA), are being assessed as a once-daily, fixed-dose combination tablet. The phase 2 C-WORTHY study showed a good safety profile and high efficacy of grazoprevir plus elbasvir with or without ribavirin for 12 weeks in monoinfected and co-infected patients with HCV genotype 1 infection, with or without cirrhosis.13, 17 The C-EDGE CO-INFECTION study assessed the efficacy, safety, and tolerability of a fixed-dose combination of grazoprevir plus elbasvir in patients with HIV and HCV co-infection.
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Study design and participants
The C-EDGE CO-INFECTION study was an uncontrolled, non-randomised, open-label, single-arm, multicentre study. Treatment-naive patients older than 18 years with chronic HCV genotype 1, 4, or 6 infection and baseline HCV RNA of at least 10 000 IU/mL were enrolled. All patients were co-infected with HIV-1 and either naive to antiretroviral therapy (ART) or on stable ART with tenofovir or abacavir, and either emtricitabine or lamivudine plus raltegravir, dolutegravir, or rilpivirine for at least 8
Results
Patients were enrolled between June 11, 2014, and Aug 29, 2014, at 37 centres in nine countries across Europe, the USA, and Australia. 261 patients were screened; 218 were enrolled and received grazoprevir plus elbasvir for 12 weeks (figure 1; table 1).
In the overall population, 210 (96%) achieved SVR12 (95% CI 92·9–98·4), exceeding the historical reference rate of 70% (table 2). Five patients relapsed after having undetectable HCV RNA concentrations at the end of treatment (table 3). All
Discussion
This single-arm, open-label trial showed the efficacy of 12 weeks of treatment with a fixed-dose combination of grazoprevir plus elbasvir in patients with HIV infection and HCV genotype 1, 4, or 6 co-infection. The overall SVR12 rate was 95% in the primary analysis and 97% in the per-protocol analysis. In the C-EDGE Treatment-Naive trial19 in patients with HCV monoinfection, SVR12 was achieved in 95% of patients, thus supporting the growing body of data suggesting that patients with HCV and HIV
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