Pharmacokinetics of atazanavir in HIV-HCV co-infected patients with or without cirrhosis
Abstract number: 1734_193
Gatti F., Loregian A., Nasta P., Pagni S., Prestini K., Matti A., Parisi S.G., Biasi L., Puoti M., Boldrin C., Palù G., Carosi G.
Objectives: To evaluate the influence of liver cirrhosis on atazanavir (ATV) pharmacokinetics (PK) in HIV/HCV co-infected patients (pts) treated with atazanavir ± ritonavir (ATV 400 mg QD or ATV/r 300/100 mg QD).
Methods: 14 HIV/HCV co-infected pts receiving ATV/r 400/100 mg QD and 4 pts receiving ATV 400 mg QD were included. According to liver stiffness (LS) value obtained by fibroscan® at the moment of PK determination or histological diagnosis patients were classified in 2 groups:
NC, no cirrhosis (10 pts); LS < 12 kPa or Knodell fibrosis score (Kfs) 13;
C, cirrhosis (8 pts); LS ≥12 kPa or Kfs 4.
ATV plasma levels were determined by High Performance Liquid Chromatography.
Samples for the 24 hour PK curve were collected at t = 01.53.58 h at the steady state. C trough (Ct) was determined before the daily dose. PK analysis of plasma ATV concentrationtime data were conducted using non-compartmental methods with WinNonlinProfessional software, version 4.1. The area under the concentrationtime curve during a dosing interval (AUC024) was calculated using the log linear trapezoidal method. Results are expressed as median and interquartiles.
Parametric and non parametric tests have been used for comparison of continuous variables between groups when appropriate and linear regression analysis to test correlation between variables (p < 0.05 was considered as significant).
Results: All but one pts had HIV-RNA <50 copies/mL and 14/18 pts were on TDF+3TC/FTC. Median (range) LS was 6 (59) kPa for NC and 19 (1321.5) for C pts (p = 0.0005). Median (range) ATV Ct level was 390 (180475) ng/mL in C and 525 (170620) ng/mL in NC pts (p = NS). Median ATV AUC was 32,833 (22,48039,707) ng·h/mL in C and 25,156 (16,92950,194) ng·h/mL in NC (p = NS); no statistically significant correlation was found between AUC and LS (p = 0.12).
The analysis restricted to the pts taking ATV/r showed no statistically significant difference of Ct or AUC between groups, but a significant inverse correlation was found between AUC and LS (p = 0.03) and a trend toward a significant correlation was found between Ct and LS (p = 0.06).
Conclusions: The slight reduction in Ct observed in cirrhotic patients with mild disease could be related to the reduction and/or diversion of the liver blood flow related to initial portal hypertension associated to increased liver stiffness and would probably become significant in case of severe cirrhosis; this could also explain the inverse correlation found between AUC/Ct and LS.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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