Liver toxicity and plasma drug levels of lopinavir in HIV/HCV co-infected patients according to the degree of liver fibrosis

Abstract number: P785

Moya J., Casado J.L., Moreno A., Aranzabal L., Gutierrez C., Perez-Elias M., Moreno S.

Objectives: HCV co-infection is a well known risk factor for developing hepatotoxicity in HIV-infected patients receiving HAART. However, few data exist about liver toxicity with r/lopinavir and the influence of plasma drugs levels, especially in patients with different stages of HCV disease.

Methods: Prospective cohort study of 51 HIV/HCV co-infected patients who underwent a liver biopsy and who received lopinavir as the third drug regimen. Liver fibrosis was staged using a scoring system of 0 (no fibrosis) to 4 (cirrhosis). Hepatotoxicity was defined as an increase in AST/ALT levels over five times the upper limit of normal, or a 3.5-fold increase if baseline levels were abnormal, with or without clinical symptoms of liver toxicity. Plasma through levels of lopinavir were determinated by HPLC in all the cases.

Results: Mean age was 41 yrs, 73% were male, and 73% were former IDUs. Of note, 58% of patients had a prior diagnosis of AIDS. Mean estimated time of HCV infection was 17.6 yrs, mean HCV viral load was 1.298235 UI/ml, and the predominant HCV genotypes were 1 and 3. Median plasma drug levels of lopinavir were 7315 ng/ml (638–11206), with differences according to the stage of fibrosis (8114, 6614, 6008, and 4412 ng/ml for fibrosis stage 1 to 4, respectively). Notably, in three cirrhotic patients with an advanced stage of disease (MELD scale >11), median plasma through levels were 881 ng/ml. During an accumulated time of 461 months on r/lopinavir therapy, there were 5 cases of hepatotoxicity. In these patients, plasma trhough levels of lopinavir were similar to those observed in patients not developing toxicity (6502 vs 7368 ng/ml).

Conclusions: The risk of liver toxicity was very low in HIV/HCV co-infected patients receiving r/lopinavir. In these patients, plasma drug levels of lopinavir showed high interpatient variability and were not associated with toxicity.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Location: Barcelona, Spain
Presentation type:
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