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.

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.