Phase 3 Trial Shows Simeprevir, Ribavirin, and Peginterferon Combination Effective in HIV/HCV Coinfection

Data indicates that a simeprevir-based therapy is efficacious in patients with HIV-1/HCV genotype 1 coinfection.

Data indicates that a simeprevir-based therapy is efficacious in patients with HIV-1/HCV genotype 1 coinfection.

Results of a phase 3 study published September 6, 2014 in the journal Clinical Infectious Disease demonstrates the efficacy of Janssen's simeprevir (Olysio) in combination with peginterferon and ribavirin in patients with genotype-1 hepatitis C and HIV-1 coinfection.

Due to the inclusion criteria used in this trial, results do not apply to patients with cirrhosis, to patients without HIV, or to patients with hepatitis C genotypes other than genotype 1.1

In the 106-patient, uncontrolled, open-label trial, patients received a 12-week treatment course consisting of a 150-mg capsule of simeprevir daily, along with peginterferon, and ribavirin. Treatment with simeprevir involves testing at various time points for response.

This approach, known as response-guided therapy, involves testing HCV RNA levels at week 4 and week 12. If HCV levels are not lower than 25 IU/mL as determined by the Roche COBAS TaqMan HCV test at these time points, treatment is discontinued early.1,2

Patients enrolled in the trial were assessed for rates of sustained viral response 12 weeks after completion of therapy (SVR12) in each of 4 groups: patients who had never received therapy for chronic HCV infection before (treatment-naïve patients), patient who had received HCV treatment in the past and who had not experienced SVR (prior null responders), patients who had attained SVR in the past and experienced a relapse (prior relapsers), and patients who had experienced a partial response with prior therapy, but who did not attain SVR at any point (prior partial responders).1

Prior relapsers experienced the highest response rate in the trial, with 86.7% achieving SVR12. SVR12 rates decreased progressively in more difficult-to-treat subpopulations, including treatment-naive patients (79.2%), prior partial responders (70%), and prior null responders (57.1%).

As in other trials with regimens containing peginterferon and ribavirin, fatigue, headache, nausea, and neutropenia were common adverse events. Serious AEs, including AEs of grade 3 or higher, occurred in 5.7% of patients in this trial.

Results of this study compare favorably with the results of PHOTON-1, in which the antiviral sofosbuvir was used in combination with ribavirin over a 24-week treatment course. In this study, SVR12 rates in patients with HIV-1 and genotype 1 HCV were 76% among treatment-naïve participants. Importantly, these results were attained without use of peginterferon, which is an important difference between the PHOTON-1 study and the current study.

With this phase 3 trial complete, Janssen may soon file for approval of simeprevir as a treatment for patients with genotype 1 HCV who also have HIV-1. These results may lead to changes in HCV guidelines, which currently only recommend simeprevir in patients with HIV/HCV coinfection as an add-on to sofosbuvir-based treatment.2,4

Reference:

  • Dieterich D, Rockstroh JK, Orkin C, et al. Simeprevir (TMC435) with Peginterferon/Ribavirin in Patients Coinfected with HCV Genotype-1 and HIV-1: A Phase III Study [published online September 6, 2014]. Clin Infect Dis. 2014.
  • OLYSIO (simeprevir) [package insert]. Titusville, NJ: Janssen Therapeutics; 2014.
  • Sulkowski MS, Naggie S, Lalezari J, et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. JAMA. 2014;312(4):353-361.
  • IDSA/AASLD HCV Guidelines. Unique patient populations. http://www.hcvguidelines.org/full-report/unique-patient-populations. Updated September 2, 2014. Accessed September 8, 2014.