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

Stephanie Dominguez, Jade Ghosn*, Gilles Peytavin, Marguerite Guiguet, Roland Tubiana, Marc Antoine Valantin, Robert Murphy, François Bricaire, Yves Benhamou, Christine Katlama

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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 (Cmin) 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. Cmin 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 Cmin values were not different in the two groups, except for lopinavir, with a lower Cmin 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 Cmin than HIV-infected patients; median Cmin 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 Cmin 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.

Original languageEnglish (US)
Article numberdkq320
Pages (from-to)2445-2449
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume65
Issue number11
DOIs
StatePublished - Sep 2 2010

Keywords

  • Antiretroviral therapy
  • Chronic hepatitis C
  • HIV
  • Liver disease
  • Pharmacology
  • Safety
  • Therapeutic drug monitoring
  • Toxicity

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Impact of hepatitis C and liver fibrosis on antiretroviral plasma drug concentrations in HIV-HCV co-infected patients: The HEPADOSE study'. Together they form a unique fingerprint.

Cite this