title: Maintenance of indinavir by dose adjustment in HIV-1-infected patients with indinavir-related toxicity.
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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine I, University of Bonn, Sigmund Freud Str. 25, 53105, Bonn, Germany. j-c.wasmuth@uni-bonn.de
authors: J-C
authors: JC
authors: Wasmuth
authors: I
authors: I
authors: Lambertz
authors: E
authors: E
authors: Voigt
authors: M
authors: M
authors: Vogel
authors: C
authors: C
authors: Hoffmann
authors: D
authors: D
authors: Burger
authors: J K
authors: JK
authors: Rockstroh
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D005858:Germany; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D019469:Indinavir / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced; D008875:Middle Aged; D011446:Prospective Studies; D019438:Ritonavir / Q000008:administration & dosage*; D012720:Severity of Illness Index; D012871:Skin Diseases / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D019438:Ritonavir
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