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

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.