Effective HCV therapy in HIV coinfected patients
Posted on April 15, 2015
PHOTON-2 study results confirm the findings of PHOTON-1: sofosbuvir and ribavirin provide high rates of sustained virological response in patients with HCV genotypes 1–3 who are co-infected with HIV.
PHOTON-2 also provides the first clinical evidence that an interferon-free regimen can be highly effective for treatment of HCV genotype 4 in patients co-infected with HIV.
HIV exacerbates the morbidity of patients with HCV, even in those receiving highly active antiretroviral therapy. Successful HCV therapy in coinfected patients is associated with a reduction in liver-related events, and in HIV progression and mortality not related to liver disease. Results of the PHOTON-1 study indicated that treatment-naïve coinfected patients with HCV genotypes 1–3 and treatment-experienced coinfected patients with HCV genotypes 2 and 3 achieved high rates of sustained virological response (67–94%) after administration of sofosbuvir plus ribavirin (Sulkowski MS et al. JAMA. 2014;312:353–361). The results of the recently published, open-label, non-randomized, multicenter, uncontrolled PHOTON-2 study validate and expand upon those of PHOTON-1, and also provide the first clinical evidence that sofosbuvir plus ribavirin, an interferon-free regimen, can be highly effective for treatment of patients co-infected with HCV genotype 4 (Molina JM et al. Lancet. 2015 Mar 21;385(9973):1098-1106).
This clinical trial article is available for free for a limited time in the specialist section of the American Journal of Medicine Hepatitis C Resource Center. Click here!
- All patients received a once-daily oral dose of sofosbuvir 400 mg in combination with twice-daily oral weight-based ribavirin (1000 mg in patients with bodyweights <75 kg and 1200 mg in those with weights ≥75 kg). Treatment duration was 24 weeks for all patients except treatment naïve patients with HCV genotype 2, who were treated for 12 weeks.
Between February 7, 2013 and July 9, 2013, 275 eligible patients with a chronic infection with HCV genotypes 1–4 and HIV-1 were enrolled in the PHOTON-2 study. Patients in all treatment groups had rapid and substantial declines in serum HCV RNA concentrations after start of treatment.
- Overall, 54 patients (20%) had cirrhosis, with a higher prevalence in treatment-experienced patients than in treatment-naïve patients
- Across treatment groups, 89–100% of patients were taking antiretroviral therapy
- 112 treatment-naïve patients with HCV genotype-1
- Primary endpoint: SVR12: 85% (95% CI 77–91)
- Response rate in patients with HCV genotype 1a: 83% (84 of 100 patients)
- Response rate in patients with HCV genotype 1b: 91% (10 of 11 patients)
- 19 treatment-naïve and 6 treatment-experienced patients with HCV genotype-2
- SVR12: 88% (95% CI 69–98)
- 17 of the treatment naïve patients (89%) and 5 of the treatment-experienced patients (83%) achieved SVR12
- 58 treatment-naïve patients 49 treatment-experienced patients with HCV genotype-3
- SVR12: 89% (95% CI 81–94)
- 52 of the treatment-naive patients (91%) and 42 of the treatment-experienced patients (86%) achieved SVR12
- 31 treatment-naïve patients with HCV genotype-4
- SVR12: 84% (95% CI 66–95)
- No sofosbuvir-resistance mutations emerged in those patients who experienced HCV viral relapse
- Four patients (1%) receiving antiretroviral treatment had a transient HIV viral breakthrough; however, none required changes in antiretroviral regimen
Overall, 246 patients (90%) reported at least one adverse event. Six patients (2%)—all receiving the 24-week regimen—discontinued all study treatment because of an adverse event and 15 (5%) had a serious adverse event. Four patients (1%) had serious adverse events regarded as related to study treatment (2 patients had anemia, 1 patient developed thrombocytopenia and petechiae, and 1 patient had mania); all these events resolved by the end of follow-up. No patients died during the study.
- The incidence of adverse events was similar between groups. The most common adverse events were fatigue, insomnia, asthenia, and headache. Most adverse events were mild or moderate in severity. The most common laboratory abnormalities were decreased hemoglobin concentration and increased total bilirubin.
The results of the PHOTON-2 study demonstrate that an interferon-free regimen of sofosbuvir plus ribavirin for 12 or 24 weeks can be highly effective for treatment of treatment-naive or treatment experienced patients co-infected with HIV and HCV genotypes 1–4.