SVR12 Rates Higher in Treatment-Naïve, Noncirrhotic Patients with HCV/HIV
SAN DIEGO, CA—Treatment with boceprevir and pegylated interferon/ribavirin (PIFN/R) in persons co-infected with hepatitis C virus (HCV)and HIV resulted in higher sustained virologic response (SVR) rates at 12 weeks if they were treatment-naïve without cirrhosis, Phase 3 trial results reported at IDWeek 2015 have found.
The SVR rates were also higher than those observed at 24 weeks in the A5178 study, which examined the effects of PIFN/R maintenance therapy on fibrosis progression in patients failing to respond to 12 weeks of treatment with PIFN/R. However, SVR12 rates “were lower than those reported in other boceprevir studies, including a Phase 2 co-infection study and in studies with newer directly acting antivirals in co-infected patients,” noted Adeel Butt, MD, MS, of the University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania and of the Hamad Healthcare Quality Institute in Doha, Qatar.
Subjects with chronic HCV genotype 1 (treatment-naïve or treatment-experienced) and HIV-1 infection were enrolled in the prospective open-label trial. Patients were required to be stable on combination antiretroviral therapy (cART) with efavirenz, raltegravir, boosted lopinavir, atazanavir, or darunavir plus dual nucleoside/nucleotide reverse transcriptase inhibitor backbone (NRTI) therapy with HIV-1 RNA <50 copies/mL (c/mL); or no cART with HIV-1 RNA <50,000c/mL. Study subjects received PIFN/R for 4 weeks; boceprevir 800mg three times daily was then added.
Those who were treatment-naïve without cirrhosis received triple therapy for 24 weeks or triple therapy for 32 weeks followed by 12 weeks of PIFN/R based on Week 8 response.
“Non-cirrhotic treatment-experienced subjects were treated the same as treatment-naïve who failed to clear HCV RNA by Week 8,” Dr. Butt noted. “All treatment-naïve and treatment-experienced cirrhotic subjects received 44 weeks of triple therapy after lead-in.”
A total of 135 treatment-naïve and 127 treatment-experienced subjects were enrolled; 135 and 122, respectively, were included in the analysis.
Among the treatment-naïve subjects, 82% were male, median age was 51 years, 42% were Caucasian, and 54% were black. Median baseline HCV RNA was 6.7 log10 IU/mL; CD4 count was 646 cells/mm3; and 98% were on cART (43% efavirenz, 35% raltegravir, 3% lopinavir, 13% atazanavir, 4% darunavir). Among the treatment-experienced subjects, 76% were male, median age was 53 years, 48% were Caucasian, 43% were blacks. Median baseline HCV RNA was 6.9 log10 IU/mL, CD4 count was 622 cells/mm3, and 95% were on cART (42% efavirenz, 37% raltegravir, 3% lopinavir, 8% atazanavir, 5% darunavir).
For the treatment-naïve overall group, Week 8 response was 36%, end treatment response was 47%, and SVR12 was 36% (95% CI: 28%, 44%). For the treatment-naïve noncirrhotic group, responses were 37%, 49%, and 37% (95% CI: 29%, 46%) and, for the treatment-naïve cirrhotic group, 28%, 39%, and 28% (95% CI: 13%, 51%), respectively.
For the treatment- experienced overall group, Week 8 response was 23%, end treatment response was 38%, and SVR12 was 30% (95% CI: 23%, 39%). For the treatment-experienced noncirrhotic group, responses were 19%, 36%, and 32% (95% CI: 23%, 43%) and, for the treatment-experienced cirrhotic group, 32%, 42%, and 26% (95% CI: 15%, 42%), respectively.
Among treatment-naïve subjects, 32% received shorter therapy, 28 weeks. One death occurred in the treatment-naïve group unrelated to study drugs. Overall, 20% of those in the treatment-naïve group and 16% in the treatment-experienced group discontinued treatment due to safety and/or tolerability.
“Boceprevir -based HCV therapy was reasonably tolerated with an expected adverse event profile,” they concluded.