STARTVerso 4: High Rates of Early Virologic Response in Hepatitis C Virus Genotype 1/HIV Co-infected Patients Treated with Faldaprevir + Pegylated Interferon and Ribavirin
Douglas Dieterich*1, V Soriano2, M Nelson3, J Rockstroh4, K Arasteh5, S Bhagani6, A Talal7, C Tural8, R Vinisko9, and J Kort9
1Mt Sinai Sch of Med, New York, NY, US; 2Hosp Carlos III, Madrid, Spain; 3Chelsea and Westminster Hosp, London, UK; 4Univ of Bonn, Germany; 5EPIMED, Vivantes Auguste-Viktoria Hosp, Berlin, Germany; 6Royal Free Hosp, London, UK; 7State Univ of New York, Buffalo, US; 8Hosp Univ Germans Trias i Pujol, Barcelona, Spain; and 9Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, US
Background: Faldaprevir (FDV; BI 201335) is an hepatitis C virus (HCV) NS3/4A protease inhibitor (PI) in late-stage clinical development for the treatment of HCV genotype 1 (GT1) infection. In this open-label, sponsor-blinded, phase III trial, the efficacy and safety of FDV + pegylated interferon alfa-2a and ribavirin (pegIFN/RBV) was assessed in individuals co-infected with HCV and HIV.
Methods: Individuals co-infected with HCV/HIV who were HCV treatment-naïve (TN) or relapsed after previous HCV therapy were randomized to receive FDV 120 or 240 mg once daily for 12 or 24 weeks, in combination with pegIFN (180 µg once weekly) and weight-based RBV for 24 or 48 weeks (response guided). Patients on efavirenz- or PI-based ART were allocated to receive FDV 240 mg or 120 mg once daily, respectively; those receiving other ART or no ART were randomized to either FDV dose. Interim data remain blinded for FDV dose. Week 4 and 12 interim data are presented.
Results: 308 patients were randomized and treated: 96% were receiving ART; for HCV therapy, 78% were TN and 22% were relapsers; 81% were male; 78% were Caucasian; 4% had F4 cirrhosis, and 13% had Fibroscan >13 kPa; 80% had baseline HCV RNA ≥800,000 IU/mL; 78% had GT1a. Virologic responses are shown (Table).
HCV RNA was BLD at week 4/week 12 in 64%/64% of patients not on ART, and in 63%/85% of patients receiving ART. The most frequent adverse events were those known for pegIFN/RBV treatment: nausea (37%), fatigue (34%), and diarrhea (29%). Serious adverse events were reported in 32 (10%) patients (including 2 deaths; none considered related to study medications). To date, 18 patients discontinued early due to adverse events. No patient on ART experienced loss of HIV RNA suppression.
Conclusions: In this interim analysis, FDV + pegIFN/RBV provided high early virologic response rates in HCV GT1 patients co-infected with HIV at weeks 4 and 12. The efficacy and safety profile was comparable to that observed in HCV mono-infected TN patients.