Determination of indinavir and nelfinavir trough plasma concentration efficacy thresholds according to virological response in HIV‐infected patients

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Abstract
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 (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. Results 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; Pr=−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. Conclusions 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.

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