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Pharmacokinetics of Boosted PI and NNRTI in HCV/HIV-co-infected Patients
Dominique Breilh*, S Guinguené, V de Lédinghen, J Toutain, J L Pellegrin, P Trimoulet, I Pellegrin, M Dupon, M C Saux, and D Neau
Ctr Hosp Univ Bordeaux, France
Background: Transient elastometry (Fibroscan) is a reproducible
method allowing evaluation of liver fibrosis by measurement of liver stiffness.
The aim of this study was to evaluate ART pharmacokinetics in HIV patients with
chronic hepatitis C virus (HCV) and to determine a relationship between ART
concentrations and liver fibrosis.
Methods: A total of 113 HCV/HIV-co-infected patients
receiving HAART containing boosted protease inhibitor (PI) or non-nucleoside
reverse transcriptase inhibitors (NNRTI) were included in the study. A liver
stiffness cut-off defined 2 groups, over or under 12 kPa. Boosted PI plasma
concentrations (Cmin and Cmax), such as lopinavir (n = 52), atazanavir (n = 37), and fosamprenavir (n = 9), and NNRTI, such as efavirenz
(EFV) (n = 19) and nevirapine (NVP) (n = 6), were compared in these 2 groups
by using a Mann Whitney test with p <0.05.
In case of difference, a relationship between ART concentrations and liver
stiffness was determined by using a Spearmann test.
Results: Considered to have a cirrhosis were 42 patients
(37%) whose liver stiffness exceeded 12 kPa. There was no statistical
difference for Cmin and Cmax between the 2 groups for all
boosted PI. The average of observed concentrations did not differ from
HIV-infected patients without HCV infection. There was a difference for NNRTI
C12h : 2.87±1.75 vs 7.27±2.41 mg/L (p =
0.017) and 3.64±2.05 vs 7.10±0.71 mg/L (p
= 0.008), respectively, for EFV and NVP and for <12 kPa and >12 kPa.
A relationship between NNRTI’s C12h and liver stiffness was found r = 0.464 and 0.763 for
EFV and NVP, respectively.
Conclusions: These preliminary findings suggest that only
NNRTI’s C12h may be elevated in HCV/HIV-co-infected patients and correlated
with liver stiffness. Further investigations will be necessary to confirm these
results. Therapeutic drug monitoring will be helpful to identify co-infected
patients at risk for toxicity.
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