"Mission Accomplished," the title given by CROI 2015 organizers for the session on hepatitis C (HCV) treatment, was premonitional. Two big phase-3 studies in HIV/HCV coinfected individuals were presented.
In the ION-4 study, 335 patients received two weeks of the first single-tablet, coformulated, once-daily, complete treatment for HCV, without interferon and ribaviron. The combination included ledipasvir (an NS5A inhibitor) and sofosbuvir (Sovaldi), both with pangenotypic activity. About 20% had compensated cirrhosis, and 28% had an IL28B CC genotype. Antiretroviral therapy included efavirenz (Sustiva, Stocrin), raltegravir (Isentress) and rilpivirine (Edurant).
In the overall analysis, 96% of the subjects were cured (321 out of 335 achieving sustained virologic response 12 weeks after completing treatment, or SVR12), with only 10 relapses. There were no differences in efficacy in treatment-naive patients versus treatment-experienced patients, with or without cirrhosis. All subjects with relapse had an unfavorable IL28B genotype. Of importance, the HCV viral decay showed no correlation with response, something that was also reported with other HCV treatment strategies. This could mean that there's no need to monitor the HCV viral load during the 12 weeks of therapy for clinical purposes.
The second presentation in the session was the ALLY-2 study that treated 203 patients with daclatasvir (NS5A inhibitor) and sofosbuvir. Treatment-naive patients were randomized to receive 12 or 8 weeks of treatment, and treatment-experienced patients received 12 weeks. Once again, impressive efficacy was seen with 12 weeks of treatment in both treatment-naive (97% with SVR12) or treatment-experienced individuals (98% SVR12). However, the 8-week arm faired less well, with only a 76% SVR12 rate.
The sample size was limited (only 52 patients) but showed interesting findings: 10 subjects experienced virologic relapse, while a lower response was seen in subjects with high HCV viral load and in those treated with darunavir. Baseline characteristics appear to correlate with HCV treatment response. The darunavir issue was likely due to drug-drug interactions.
At the current prices of HCV treatments and taking into account their restriction, these errors should not occur, and coinfected subjects should only be treated with regimens that had demonstrated an absence of drug-drug interactions and proven in clinical trials. Otherwise, switching their antiretroviral therapy regimen during the three months of HCV treatment to non-interacting agents should be considered.
Which other studies presented at CROI 2015 will have lasting impact? Read more of Llibre and Young's top picks.
Josep M. Llibre, M.D., is in the HIV Unit of the "Lluita contra la SIDA" Foundation at University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. Llibre has received funding for research or payment for conferences or participation on advisory boards from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare.
Benjamin Young, M.D., Ph.D., is vice president and chief medical officer of the International Association of Providers of AIDS Care based in Washington, D.C., and an adjunct professor at the Josef Korbel School of International Studies at the University of Denver. Young has received consulting or speaking fees from Bristol-Myers Squibb, Cerner Corporation, Gilead Sciences, GlaxoSmithKline, Merck & Co., Monogram Biosciences, and ViiV Healthcare. He has received research funding from Bristol-Myers Squibb Company, Cerner Corporation, Gilead Sciences, GlaxoSmithKline, Merck & Co., and ViiV Healthcare.