Introduction: Combination of Daclatasvir (DCV) and Sofosbuvir (SOF) is widely used in HIV/HCV co-infection because of few drug-drug interactions with HAART. Anyway, data on safety and efficacy in co-infected population with advanced liver disease are still scarce. We report preliminary data from a cohort of co- infected patients treated with DCV+SOF in a compassionate use program (CUP) in Italy. Methods: CUP enrolled adult patients with liver cirrhosis and/or high risk of death within 12 months without other treatment options. All patients received SOF 400 mg QD + DCV (dose depending on comedications); ribavirin (RBV) use was at physician’s discretion. Results: 58 patients were enrolled; to date, 41 have data available for SVR12 analysis. 74.1% of patients were male; median age was 52 years (IQR 50-54). 20.7% had previous AIDS; baseline HIV-RNA was undetectable in 98.3%. HAART regimens were heterogeneous: the most used were 2NRTIs+INSTI (31.4%) and INSTI+PI (29.6%). Most patients were infected by genotype 1a (46.6%) and 3 (31%); 8.6% were also HBV co- infected. Cirrhosis was present in 93.1% of subjects (CPT A 42.6%, B 42.6%, C 5.6%) with a median MELD of 12 (IQR 9-13). 13.8% were waitlisted for liver transplant (LT) and 12.1% were LT recipients. All patients completed 24 weeks of treatment, except 3 (5.2%) who discontinued earlier: 1 at week 20 because of liver toxicity (and died 12 weeks later), 1 at week 13 (dead of cholestatic fibrosing hepatitis), 1 had LT at week 20 and reached SVR12. 1 patient died during follow-up for a car accident. SVR12 rate in ITT analysis was 92.7% in the overall population (92% in GT1, 92.3% in GT3, 100% in GT4), 83.3% in LT recipients and 100% in LT candidates. RBV was used in 74.1% of patients: of these, 24.3% developed haemoglobin levels <10 g/dl, 10.8% introduced erythropoietin and 35% discontinued RBV. 30% of patients developed total bilirubin >4 mg/dl. 1 patient had HIV virologic failure (>400 copies/ml), but was re- suppressed by switching HAART. Conclusions: These preliminary data show that DCV + SOF +/- RBV is effective in this difficult- to-treat population, with high SVR12 rate and an acceptable safety profile, even if management of anemia and liver-related complications can be challenging. HAART management in combination with anti-HCV therapy was not a significant issue.
Daclatasvir + Sofosbuvir +/- Ribavirin in HIV/HCV co-infected patients with advanced liver disease: preliminary data from the Italian Compassionate Use Program
D. Segala;G. Verucchi
2016
Abstract
Introduction: Combination of Daclatasvir (DCV) and Sofosbuvir (SOF) is widely used in HIV/HCV co-infection because of few drug-drug interactions with HAART. Anyway, data on safety and efficacy in co-infected population with advanced liver disease are still scarce. We report preliminary data from a cohort of co- infected patients treated with DCV+SOF in a compassionate use program (CUP) in Italy. Methods: CUP enrolled adult patients with liver cirrhosis and/or high risk of death within 12 months without other treatment options. All patients received SOF 400 mg QD + DCV (dose depending on comedications); ribavirin (RBV) use was at physician’s discretion. Results: 58 patients were enrolled; to date, 41 have data available for SVR12 analysis. 74.1% of patients were male; median age was 52 years (IQR 50-54). 20.7% had previous AIDS; baseline HIV-RNA was undetectable in 98.3%. HAART regimens were heterogeneous: the most used were 2NRTIs+INSTI (31.4%) and INSTI+PI (29.6%). Most patients were infected by genotype 1a (46.6%) and 3 (31%); 8.6% were also HBV co- infected. Cirrhosis was present in 93.1% of subjects (CPT A 42.6%, B 42.6%, C 5.6%) with a median MELD of 12 (IQR 9-13). 13.8% were waitlisted for liver transplant (LT) and 12.1% were LT recipients. All patients completed 24 weeks of treatment, except 3 (5.2%) who discontinued earlier: 1 at week 20 because of liver toxicity (and died 12 weeks later), 1 at week 13 (dead of cholestatic fibrosing hepatitis), 1 had LT at week 20 and reached SVR12. 1 patient died during follow-up for a car accident. SVR12 rate in ITT analysis was 92.7% in the overall population (92% in GT1, 92.3% in GT3, 100% in GT4), 83.3% in LT recipients and 100% in LT candidates. RBV was used in 74.1% of patients: of these, 24.3% developed haemoglobin levels <10 g/dl, 10.8% introduced erythropoietin and 35% discontinued RBV. 30% of patients developed total bilirubin >4 mg/dl. 1 patient had HIV virologic failure (>400 copies/ml), but was re- suppressed by switching HAART. Conclusions: These preliminary data show that DCV + SOF +/- RBV is effective in this difficult- to-treat population, with high SVR12 rate and an acceptable safety profile, even if management of anemia and liver-related complications can be challenging. HAART management in combination with anti-HCV therapy was not a significant issue.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
