Impact of hepatitis C and liver fibrosis on antiretroviral plasma drug concentrations in HIV-HCV co-infected patients: the HEPADOSE study

J Antimicrob Chemother. 2010 Nov;65(11):2445-9. doi: 10.1093/jac/dkq320. Epub 2010 Sep 2.


Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alkynes
  • Anti-Retroviral Agents / administration & dosage*
  • Anti-Retroviral Agents / pharmacokinetics*
  • Benzoxazines / administration & dosage
  • Benzoxazines / pharmacokinetics
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • Cross-Sectional Studies
  • Cyclopropanes
  • Dideoxynucleosides / administration & dosage
  • Dideoxynucleosides / pharmacokinetics
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / physiopathology
  • Humans
  • Liver Cirrhosis / physiopathology*
  • Lopinavir
  • Male
  • Middle Aged
  • Plasma / chemistry*
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / pharmacokinetics


  • Alkynes
  • Anti-Retroviral Agents
  • Benzoxazines
  • Cyclopropanes
  • Dideoxynucleosides
  • Pyrimidinones
  • Lopinavir
  • efavirenz
  • abacavir