Impact of hepatitis C and liver fibrosis on antiretroviral plasma drug concentrations in HIV-HCV co-infected patients: the HEPADOSE study.
OBJECTIVE
To compare plasma antiretroviral concentrations in HIV-HCV co-infected and in matched HIV mono-infected patients.


METHODS
This was a cross-sectional, observational study. Antiretroviral trough concentrations (C(min)) in plasma were measured in HIV-HCV co-infected patients with liver disease documented by liver biopsy, matched with HIV mono-infected patients according to gender and antiretroviral treatment. C(min) values in serum were measured using an HPLC method. Statistical analysis was performed using the Wilcoxon test.


RESULTS
Seventy-three HIV-HCV co-infected patients and 66 HIV-infected patients were enrolled; 70% of patients were receiving a protease inhibitor (PI)- and 30% a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. Among the 73 co-infected patients, 27 had a fibrosis score (Fibrotest(®)) of F4. Abacavir was the only nucleoside reverse transcriptase inhibitor whose trough concentrations differed between the co-infected and mono-infected groups. PI median plasma C(min) values were not different in the two groups, except for lopinavir, with a lower C(min) in the co-infected group than in the HIV-infected group (median 3673 versus 5990 ng/mL, P=0.04), and nelfinavir, with significantly higher concentrations in the co-infected group. Seventy-five percent of co-infected patients scoring F4, 33% of those scoring F0-F3 and 12% of HIV-infected patients were underdosed (P=0.02). Co-infected patients receiving an NNRTI had a higher plasma C(min) than HIV-infected patients; median C(min) was 3583 versus 1494 ng/mL (P=0.025) and 5331 versus 3954 ng/mL (P=0.10) for efavirenz and nevirapine, respectively. Overall, there was a greater proportion of co-infected patients with high concentrations of both NNRTIs (15/23) compared with HIV mono-infected patients (5/21) (P=0.008), especially in co-infected patients with an advanced liver fibrosis stage.


CONCLUSIONS
Median plasma C(min) values differed significantly between HIV and HIV-HCV co-infected patients for abacavir, lopinavir and efavirenz. NNRTIs were strongly overdosed in HIV-HCV co-infected patients.
Dominguez
Stephanie
S
AP-HP, Département de Maladies Infectieuses et Tropicales, INSERM U720, CHU Pitié-Salpêtrière, Paris, France.
Ghosn
Jade
J
Peytavin
Gilles
G
Guiguet
Marguerite
M
Tubiana
Roland
R
Valantin
Marc Antoine
MA
Murphy
Robert
R
Bricaire
François
F
Benhamou
Yves
Y
Katlama
Christine
C
D000328:Adult; D000368:Aged; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology*; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics; D000099227:Abacavir
D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D061466:Lopinavir; D011744:Pyrimidinones; D000099227:Abacavir; C098320:efavirenz