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Determination of indinavir and nelfinavir trough plasma concentration efficacy thresholds according to virological response in HIV‐infected patients
Author(s) -
Duval X,
Peytavin G,
Albert I,
Bénoliel S,
Ecobichon JL,
BrunVézinet F,
Mentré F,
Leport C,
Vildé JL
Publication year - 2004
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2004.00226.x
Subject(s) - nelfinavir , indinavir , medicine , trough (economics) , human immunodeficiency virus (hiv) , trough concentration , virology , plasma concentration , viral load , pharmacology , antiretroviral therapy , pharmacokinetics , macroeconomics , economics
Background There is evidence to suggest a pharmacokinetic–pharmacodynamic relationship in HIV‐infected patients receiving protease inhibitor (PI)‐containing highly active antiretroviral therapy (HAART); however, the effective trough PI plasma concentrations achieved have not been precisely determined. Methods The relationship between HIV viral load and concomitant PI trough plasma concentration ( C trough ) was evaluated in 101 patients receiving at least 4 months of thrice daily indinavir (IDV)‐containing ( n =68) or nelfinavir (NFV)‐containing ( n =33) HAART. The more discriminating C trough efficacy thresholds were determined statistically for each PI by using the raw C trough and the time‐corrected C trough , using the precise delay since the last PI intake and the half‐life of each PI. Results For IDV ( P= 0.002) and NFV ( P= 0.019) median C trough levels were higher in patients with undetectable viral load [0.23 mg/L ( n =30) and 2.3 mg/L ( n =16) respectively] than in patients with detectable viral load [0.11 mg/L ( n =38) and 0.6 mg/L ( n =17) respectively]. C trough levels of IDV ( r= −0.45; P <0.0001) and NFV ( r= −0.43; P =0.011) were correlated with the concomitant viral load. The more discriminating C trough efficacy thresholds were estimated statistically as 0.12 mg/L for IDV and 0.5 mg/L for NFV. When C trough values were time‐corrected, the C trough efficacy thresholds, 8 h after the last intake, were 0.15 mg/L for IDV and 0.65 mg/L for NFV. Conclusions These results support the importance of achieving minimal effective C trough to improve the virological efficacy of PI‐containing HAART, and specify the target concentrations for IDV and NFV.