Dose-Response Effect of Protease Inhibitors?
Antiretroviral concentrations have been shown to be an independent predictor of virologic response in both treatment naïve- and experienced subjects
Maintaining therapeutic antiretroviral concentrations (via good adherence, management of drug interactions) is critical
Notes:
- Potential consequences of antiretroviral interactions:
2) decreased antiviral activity
- Achieving adequate drug concentrations is a significant factor in determining the success or failure of current as well as future highly active combination antiretroviral therapy. Reports of dose-response relationships for protease inhibitors and NNRTIs are emerging.
- However, the exact nature of these relationships are not yet fully characterized. Observations have often been based on retrospective, uncontrolled studies involving small numbers of patients. Many studies have not controlled for variables such as viral susceptibility, patient heterogeneity, drug doses, and concomitant antiretroviral therapy:
- Unanswered questions include:
- which pharmacokinetic parameter is most predictive of response: different studies have looked at different pharmacokinetic parameters (e.g., Cmax, Cmin, AUC, etc). More recently, interest has focused on incorporating pharmacokinetic and virologic parameters into a predictive variable, such as the Inhibitory Quotient (IQ).
- which patients will benefit from therapeutic drug monitoring
- which drugs? Does a dose-response relationship exist for all protease inhibitors (and/or NNRTIs)?