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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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