Therapeutic drug monitoring of nelfinavir and indinavir in treatment-naive HIV-1-infected individuals.
BACKGROUND
Both virological failure and the toxicity of HIV protease inhibitors have been related to interindividual variability of plasma drug concentrations. Therapeutic drug monitoring (TDM) offers the possibility to detect patients with drug concentrations outside therapeutic ranges, who can subsequently benefit from dose modifications.


METHODS
ATHENA was a randomized controlled clinical trial. Subjects were randomly assigned to either a TDM group, in which the results of drug concentration measurements plus advice were reported to their treating physician, or to a control group for whom TDM results were not reported. This analysis refers to treatment-naive patients who started a regimen containing indinavir or nelfinavir before November 1999.


RESULTS
A total of 147 patients were randomly assigned: 92 to nelfinavir, 55 to indinavir. After one year of follow-up significantly fewer patients in the TDM group had discontinued nelfinavir or indinavir than in the control group: 17.4 versus 39.7%. This was mainly driven by a significantly lower rate of discontinuation because of virological failure in nelfinavir patients: 2.4% in the TDM group versus 17.6% in the control group, and by a non-significant difference in the rate of discontinuation because of toxicity in indinavir patients: 14.3% in the TDM group versus 29.6% in the control group. In a non-completer equals failure analysis of all randomized patients, the TDM group showed a significantly higher proportion of patients with a viral load below 500 copies after 12 months of treatment (78.2 versus 55.1%).


CONCLUSIONS
TDM of nelfinavir and indinavir in treatment-naive patients improves treatment response.
Burger
David
D
Department of Clinical Pharmacy, University Medical Centre, Nijmegen, the Netherlands. d.burger@akf.umcn.nl
Hugen
Patricia
P
Reiss
Peter
P
Gyssens
Inge
I
Schneider
Margriet
M
Kroon
Frank
F
Schreij
Gerrit
G
Brinkman
Kees
K
Richter
Clemens
C
Prins
Jan
J
Aarnoutse
Rob
R
Lange
Joep
J
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000097:blood / Q000627:therapeutic use*; D011446:Prospective Studies; D019562:Viral Load
D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir