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

  • Clinical Trial
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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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

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Acknowledgements

We thank the patients and investigators who took part in the trial. Participating investigators were: Dr. A. B. Jessen, Private Practice Berlin (three patients); Dr. E. Lauenroth-Mai, Private Practice Berlin (two patients); B. Bieniek, Private Practice Berlin (one patient); Dr. C. Mayr, Private Practice Berlin (one patient); Dr. L. Weitner IPM Study Center of Hamburg (one patient)

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Authors and Affiliations

  1. Department of Medicine I, University of Bonn, Sigmund Freud Str. 25, 53105, Bonn, Germany

    J.-C. Wasmuth, I. Lambertz, E. Voigt, M. Vogel & J. K. Rockstroh

  2. University of Schleswig Holstein, Campus Kiel, Kiel, Germany

    C. Hoffmann

  3. Department of Clinical Pharmacy, University Medical Centre Nijmegen, Nijmegen, The Netherlands

    D. Burger

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  1. J.-C. Wasmuth
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  2. I. Lambertz
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  3. E. Voigt
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  4. M. Vogel
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  5. C. Hoffmann
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  6. D. Burger
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  7. J. K. Rockstroh
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Correspondence to J.-C. Wasmuth.

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Wasmuth, JC., Lambertz, I., Voigt, E. et al. Maintenance of indinavir by dose adjustment in HIV-1-infected patients with indinavir-related toxicity. Eur J Clin Pharmacol 63, 901–908 (2007). https://doi.org/10.1007/s00228-007-0343-z

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  • DOI: https://doi.org/10.1007/s00228-007-0343-z

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