Liver Toxicity of Antiretroviral Combinations Including Fosamprenavir Plus Ritonavir 1400/100 mg Once Daily in HIV/Hepatitis C Virus-Coinfected Patients

Abstract

Our objective was to evaluate the liver toxicity of antiretroviral regimens including fosamprenavir plus ritonavir (FPV/r) 1400/100 mg once daily (QD) in HIV/hepatitis C virus (HCV)-coinfected patients. This was a prospective cohort study that included 117 HIV/HCV-coinfected patients who started FPV/r 1400/100 mg QD-based antiretroviral therapy (ART) and who neither had received a previous antiretroviral regimen containing FPV nor had a past history of virologic failure while receiving protease inhibitors (PI). The primary end point of the study was the occurrence of grade 3-4 liver enzymes elevations (LEE) within 1 year after starting FPV/r QD. Factors potentially associated with grade 3-4 LEE, including baseline liver fibrosis, were analyzed. Eleven (9%) patients had a grade 3-4 LEE during the follow-up, resulting in an incidence of severe liver toxicity of 9% (95% confidence interval 4.1-14.6%). None of these cases led to FPV/r discontinuation. Baseline liver fibrosis could be assessed in 97 (83%) patients. Six of 71 patients (8%) with significant fibrosis had a grade 3-4 LEE versus 2 of 26 (8%) without significant fibrosis (p=1.0). Twenty (21%) patients had cirrhosis at baseline. There were no cases of LEE among cirrhotics. In conclusion, the incidence of severe liver toxicity after 1 year of therapy with FPV/r QD-based ART in HIV/HCV-coinfected patients is similar to what has been reported with other boosted PIs. In addition, the presence of significant fibrosis or cirrhosis was not associated with the emergence of liver toxicity. Thus, ART regimens containing FPV/r QD may be considered safe in HIV/HCV-coinfected patients, including those with cirrhosis.

Durability and Tolerability of Fosamprenavir/Ritonavir Containing Regimens in HIV-Infected Patients with or without Hepatitis B or C Co-Infection: Results from a Large French Cohort in Clinical Practice

“…Grade 3/4 liver enzyme elevation during FPV/r regimens were infrequent in the co-infected group (5.8% for ALT and 3.8% for AST) and confirm that use of FPV/r has a satisfactory safety profile in patients with HVC or HVB co-infections. Those results confirm those of observational studies with a low occurrence of hepatic adverse events in patients treated with FPV/r regimen with and without hepatitis co-infection [15,18] and are comparable to other boosted PIs [19]. Occurrence of hepatic adverse events has recently been shown more frequent with PI/r including regimen in naïve HCV co-infected patients (10.5% patients with grade 3/4 AST/ ALT elevation) [22].…”

“…In a large population of patients receiving FPV/r, the incidence of adverse hepatic events was low even in co-infected patients (0.58% and 2.63% in HCV and HBV co-infected patients, respectively) [18]. Similar results were observed in another study in which no differences between FPV/r and other boosted PIs in term of severe liver toxicity were reported [19].…”

“…The study was conducted in a large cohort of patients treated with FPV/r containing regimens (1939 person-years), including patients with and without HBV/HCV co-infections with no selective criteria on the disease severity or on other ART or HCV/HVB treatments. The global cohort as well as the group of co-infected patients are larger than those described in a recently published meta-analysis of FPV/r clinical trials [17] or than previous observational studies [15,[18][19] and include both treatment naïve and experienced patients.…”

Clinical Significance of Hyperbilirubinemia Among HIV-1–Infected Patients Treated with Atazanavir/Ritonavir Through 96 Weeks in the CASTLE Study

“…3,[9][10][11]39 Most antiretroviral regimens are safe in HIV/HCV-coinfected individuals, including those patients with cirrhosis. 35,40 The prevalence of symptoms of jaundice or scleral icterus among patients receiving ATV/r was low overall in the CASTLE study (5%) and in patients with hyperbilirubinemia (11%). Furthermore, few patients discontinued treatment as a result of hyperbilirubinemia, jaundice, or icterus, and none of the discontinuations were between weeks 48 and 96.…”

EFV/FTC/TDF-Associated Hepatotoxicity: A Case Report and Review

“…6,7,15,16 Other groups have found an association with female sex and antiretroviral-naïve patients undergoing their first regimen, 11 or if their regimen contains a protease inhibitor. 17 Lamivudine and ritonavir have also been implicated.…”