Safety of Atazanavir (Reyataz) in HIV-HBV and HIV-HCV Coinfected Patients with Pre-existing Liver Disease

The degree of pre-existing liver fibrosis correlates with the risk of liver toxicity in HIV-HCV coinfected patients on antiretroviral therapy. However, there is less research on patients with liver cirrhosis, as well as on ritonavir-boosted atazanavir (Reyataz), one of the newer protease inhibitors.

Therefore, as reported at the recent 4th International AIDS Society Conference on HIV Treatment, Pathogenesis, and Prevention in Sydney, Australia (July 22-25, 2007), researchers performed a study to investigate the hepatic effects of regimens containing atazanavir/ritonavir in HIV positive patients coinfected with hepatitis B or C.

This retrospective cohort study included 189 HIV-infected patients who started taking atazanavir (300 mg) plus ritonavir (100 mg) once daily. Among this group, 185 were coinfected with HCV and 14 were coinfected with HBV. The pre-existing degree of liver fibrosis was known for 112 patients (59%) -- via liver biopsy in 49 subjects, transient elastometry (FibroScan) in 31, and blood markers of fibrosis (APRI plus Forns index) in 32.

Results

• After a median follow-up of 11 months, 12 of 189 patients (6.3%) developed grade 3-4 (serious to severe) transaminase (ALT and/or AST) elevations.

• The incidence of transaminase elevation was 7.98 per 100 person-years.

• 28 subjects (14.8%) developed grade 4 total bilirubin elevation.

• The incidence of total bilirubin elevation was 19.05 per 100 person-years.

• 84 patients in whom liver fibrosis could be assessed showed significant fibrosis (> stage F2), 24 had liver cirrhosis, and 28 had minimal fibrosis (< stage F2).

• In those patients with a known fibrosis score, 8 (9.5%) of those with significant fibrosis versus just 1 (3.6%) with minimal fibrosis experienced transaminase elevations.

• Transaminase elevations were observed in 2 of 24 cirrhotic patients (8.3%) and in 3 of 56 subjects with no cirrhosis (5.4%).

• Total bilirubin elevation was observed in 8 cirrhotic patients (33%) versus 7 (13%) with no cirrhosis.

• 45 patients (25%) had APRI and Forns index values consistent with fibrosis stage > F2 at study entry, and this percentage did not change significantly during follow-up.

Conclusion

"Atazanavir/ritonavir-[containing] combinations are safe in HIV patients with viral hepatitis, including those with cirrhosis," the investigators concluded. "The presence of significant fibrosis does not increase the risk of transaminase elevation in this setting."

Hospital De Valme, Hospital Pharmacy, Seville, Spain; Hospital Virgen De La Victoria, Infectious Diseases, Malaga, Spain; Hospital Reina Sofia, Infectious Diseases, Cordoba, Spain; Hospital De Valme, Infectious Diseases, Seville, Spain.

08/10/07

Reference
L Abdel-Kader, J Santos, A Rivero, and others. Hepatic effects of atazanavir plus ritonavir (ATV/r)-based combinations in patients with hepatitis virus coinfection: relationship with pre-existing liver damage. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract MOPEA072.