European Journal of Clinical Pharmacology

, Volume 63, Issue 10, pp 901–908

Maintenance of indinavir by dose adjustment in HIV-1-infected patients with indinavir-related toxicity

Authors

    • Department of Medicine IUniversity of Bonn
  • I. Lambertz
    • Department of Medicine IUniversity of Bonn
  • E. Voigt
    • Department of Medicine IUniversity of Bonn
  • M. Vogel
    • Department of Medicine IUniversity of Bonn
  • C. Hoffmann
    • University of Schleswig Holstein, Campus Kiel
  • D. Burger
    • Department of Clinical PharmacyUniversity Medical Centre Nijmegen
  • J. K. Rockstroh
    • Department of Medicine IUniversity of Bonn
Clinical Trial

DOI: 10.1007/s00228-007-0343-z

Cite this article as:
Wasmuth, J., Lambertz, I., Voigt, E. et al. Eur J Clin Pharmacol (2007) 63: 901. doi:10.1007/s00228-007-0343-z

Abstract

Objective

Treatment with indinavir/ritonavir (IDV/RTV) is very effective but hampered by frequent development of IDV-associated adverse events (mainly nephrotoxicity and skin changes). We tested whether dose reduction of IDV guided by therapeutic drug monitoring resulted in improved tolerability without compromising antiviral efficacy.

Patients

HIV-infected patients with any IDV/RTV regimen who suffer from IDV-related adverse events were included. Viral load had to be adequately controlled for at least 2 months prior to inclusion. Dose reduction from 800 mg to 600 or 400 mg IDV b.i.d. followed a specified protocol. IDV-related toxicity and IDV plasma concentrations were monitored for 24 weeks. IDV concentrations were quantified with a validated high performance liquid chromatography method.

Results

Twenty patients were included. Reasons for inclusion were: skin abnormalities 11, nephrotoxicity five, metabolic disturbances three, and hypertension one. IDV dose could be lowered to 400 mg b.i.d. in 13, to 600 mg b.i.d. in two patients. Five patients discontinued the treatment. Overall tolerability improved with respect to incidence and severity of adverse events. Median trough concentrations decreased from 1.02 mg/l (range 0.08–7.1) at baseline to 0.48 mg/l (0.11–1.4) after 24 weeks (p = 0.03) and remained above the critical threshold of 0.1 mg/l at any time after dose reduction. There was no change of CD4 cell counts or viral suppression. There were no significant changes in other laboratory parameters (creatinine, bilirubin, triglycerides, cholesterol, blood count, and urinalysis).

Conclusion

Dose reduction of IDV improved tolerability of IDV-containing highly active antiretroviral treatment (HAART). Sufficient IDV trough concentrations were maintained in all patients as was virologic control.

Keywords

HIVHAARTIndinavirRitonavirReduced dose

Abbreviations

3TC

lamivudine

ALAT

alanine aminotransferase

ASAT

aspartate aminotransferase

AZT

zidovudine

b.i.d.

twice daily

C2h

plasma concentrations of a certain drug assessed 2 h after drug intake

CDC

Centers of Disease Control

Cmax

maximum plasma concentrations of a certain drug

D4T

stavudine

DDI

didanosine

EFV

efavirenz

gGT

gamma glutamyl transpeptidase

HAART

highly active antiretroviral therapy

HCV

hepatitis C virus

HIV

human immunodeficiency virus

IDV

indinavir

MSM

men who have sex with men

NNRTI

nonnucleoside reverse transcriptase inhibitor

RTV

ritonavir

TDF

tenofovir

Copyright information

© Springer-Verlag 2007