This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of the research investigation is to improve dosing of protease inhibitors (PIs) in HIV-infected children, leading to improved outcome and decreased adverse drug reactions. In order to do so, the protocol addresses the following specific aims:
Specific Aim 1 : Determine the prevalence of genetic variations in CYP2C19, CYP3A4, CYP3A5, and MDR-1 genes in a cohort of children and adolescents with HIV infection.
Specific Aim 2 : Evaluate the relationship of this genetic variability to the pharmacokinetic parameters (Cmin, Cmax, AUC) and toxicity (graded by the DAIDS classification) of protease inhibitors in pediatric patients with HIV infection.
Specific Aim 3 : Evaluate the impact of dose adjustment of protease inhibitors based on pharmacogeneticprofile and virtual inhibitory quotient (VIQ) on clinical outcome (measured by HIV-RNA viral load and CD4+ cell count changes) and toxicity (graded by the DAIDS classification) in pediatric patients with HIV infec
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