Background: This study was designed to assess the efficacy, safety and tolerability of a boceprevir (BOC)-containing regimen for the treatment of HCV in HCV/HIV-1 co-infected persons.
Methods: HCV treatment naïve (TN) and treatment experienced (TE) subjects with chronic HCV genotype 1 and HIV-1 infection were enrolled in a prospective, open-label, Phase 3 trial. Enrollment required either (1) stable cART with efavirenz, raltegravir, boosted lopinavir, atazanavir or darunavir plus dual NRTI backbone with HIV-1 RNA <50 copies/mL; or (2) no cART with HIV-1 RNA <50,000. All subjects received PIFN/R for 4 weeks, then BOC 800 mg TID was added. TN without cirrhosis received either (1) triple therapy for 24 weeks; or (2) triple therapy for 32 weeks followed by 12 weeks of PIFN/R based on Week 8 response. Non-cirrhotic TE subjects were treated the same as TN who failed to clear HCV RNA by Week 8. All TN and TE cirrhotic subjects received 44 weeks of triple therapy after lead-in. Early stopping rules for treatment futility for each subject were applied at weeks 12 and 24. The study was powered to conclude SVR24 >28% in TN and >10% in TE; null rates were based on the completed A5178 study on PIFN/R. We report on SVR12 results.
Results: 135 TN and 127 TE were enrolled, and 135 TN and 122 TE were included in the analysis. Among TN: 82% male, median age 51 years, 42% Caucasians, 54% Blacks, median baseline HCV RNA 6.7 log10 IU/ml, CD4 646 cells/mm3, and 98% on cART (43% EFV, 35% RAL, 3% LPV, 13% ATV, 4% DRV). Among TE: 76% male, median age 53 years, 48% Caucasians, 43% Blacks, median baseline HCV RNA 6.9 log10 IU/ml, CD4 622 cells/mm3, and 95% on cART (42% EFV, 37% RAL, 3% LPV, 8% ATV, 5% DRV). Among TN, 32% received shorter therapy (28 weeks). Week 8 (W8), End Treatment Response (ETR), and SVR12 are shown. There was one death in TN, unrelated to study drugs. Overall, 20% of TN and 16% of TE discontinued treatment due to safety/tolerability.
Conclusion: Observed SVR12 rates were higher in TN than in TE, higher in those without cirrhosis, and higher than SVR24 in A5178. SVR12 rates observed in this study were lower than those reported in other BOC studies, including a phase 2 co-infection study and in studies with newer DAAs in co-infected patients. BOC-based HCV therapy was reasonably tolerated with an expected adverse event profile.
R. Sterling, DK: Grant Investigator , Grant recipient
T. Umbleja, None
K. M. Marks, Gilead: Investigator , Research support
Merck: Investigator , Research support
B. Alston-Smith, None
W. Greaves, Merck: Employee , Salary
A. Butt, Gilead: Grant Investigator , Research grant
AbbVie: Grant Investigator , Research grant