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- Title
Determination of indinavir and nelfinavir trough plasma concentration efficacy thresholds according to virological response in HIV-infected patients.
- Authors
Duval, X.; Peytavin, G.; Albert, I.; Bénoliel, S.; Ecobichon, J.-L.; Brun-Vézinet, F.; Mentré, F.; Leport, C.; Vildé, J.-L.
- Abstract
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. The relationship between HIV viral load and concomitant PI trough plasma concentration ( Ctrough) 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 Ctrough efficacy thresholds were determined statistically for each PI by using the raw Ctrough and the time-corrected Ctrough, using the precise delay since the last PI intake and the half-life of each PI. For IDV ( P=0.002) and NFV ( P=0.019) median Ctrough 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]. Ctrough 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 Ctrough efficacy thresholds were estimated statistically as 0.12 mg/L for IDV and 0.5 mg/L for NFV. When Ctrough values were time-corrected, the Ctrough efficacy thresholds, 8 h after the last intake, were 0.15 mg/L for IDV and 0.65 mg/L for NFV. These results support the importance of achieving minimal effective Ctrough to improve the virological efficacy of PI-containing HAART, and specify the target concentrations for IDV and NFV.
- Subjects
PHARMACOKINETICS; HIV-positive persons; BLOOD plasma; PROTEASE inhibitors; ANTIRETROVIRAL agents; PATIENTS
- Publication
HIV Medicine, 2004, Vol 5, Issue 4, p307
- ISSN
1464-2662
- Publication type
Article
- DOI
10.1111/j.1468-1293.2004.00226.x