Abstract
BACKGROUND
The increasing interest in applying therapeutic drug monitoring (TDM) to antiretroviral therapy is related to the inter‐individual variation in antiretroviral pharmacokinetics. This variation may be due to certain genetic variations such as the efflux pump P‐glycoprotein MDR1 polymorphisms G2677T and C3435T.
METHOD
To facilitate the application of TDM, a real‐time PCR based genotyping method for the detection of MDR1 polymorphisms was developed in 62 HIV‐positive patients. This method was used to determine the MDR1 genotypes in both substance abuser and non‐abuser groups. The contribution of MDR1 polymorphisms to pharmacokinetic variability of antiretroviral therapy was further assessed.
RESULTS
Genotype assignments based on PCR growth curve, fluorescence melt‐curve analysis, and gel electrophoresis of PCR products were in good agreement. Although no significant difference in MDR1 polymorphism distribution was noted between substance users and non‐users (G=4.4, G2677T; G=0.6, C3435T), it appeared to be racially dependent with 75% and 92% African Americans having wild type C3435T and G2677T, versus 22% and 26% in Caucasians, respectively. A clear link between G2677T and C3435T was also noted. No relationship was observed in these initial patients between MDR1 genotypes and pharmacokinetic measures.
CONCLUSION
This method is being incorporated into the TDM program implemented in the pharmacotherapy research center.
Clinical Pharmacology & Therapeutics (2005) 79, P67–P67; doi: 10.1016/j.clpt.2005.12.243
