Multilocus genetic interactions and response to efavirenz-containing regimens: an Adult AIDS Clinical Trials Group study

@article{Motsinger2006MultilocusGI,
  title={Multilocus genetic interactions and response to efavirenz-containing regimens: an Adult AIDS Clinical Trials Group study},
  author={Alison A. Motsinger and Marylyn DeRiggi Ritchie and Robert W. Shafer and Gregory K. Robbins and Gene D Morse and Line Labbe´ and Grant R. Wilkinson and David B. Clifford and Richard T D'Aquila and Victoria A. Johnson and Richard B. Pollard and ThomasC. Merigan and Martin S. Hirsch and John P. Donahue and Richard B. Kim and David W. Haas},
  journal={Pharmacogenetics and Genomics},
  year={2006},
  volume={16},
  pages={837-845}
}
Objective For the HIV-1 reverse transcriptase inhibitor efavirenz, variant drug transporter gene ABCB1 may predict virologic response but not plasma efavirenz exposure. Conversely, variant drug metabolizing enzyme gene CYP2B6 predicts greater plasma efavirenz exposure but not virologic response. We examined whether long-term responses to efavirenz, and/or plasma efavirenz exposure, are better predicted by multilocus genetic interactions than by individual polymorphisms. Materials and methods We… 
Effect of Host Genetic Variation on the Pharmacokinetics and Clinical Response of Non-nucleoside Reverse Transcriptase Inhibitors.
TLDR
CYP2B6 genetic variants are important determinants of efavirenz and nevirapine pharmacokinetics and further studies are needed to identify the associations of CYP2B 6 genetic variants with the development of NNRTI resistant viruses.
Underlying genetic structure impacts the association between CYP2B6 polymorphisms and response to efavirenz and nevirapine
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The CYP2B6 metabolizer phenotype was significantly associated with virologic response to NNRTIs; this relationship would have been masked by simple adjustment for self-reported ethnicity, exemplify the importance of characterizing underlying genetic structure in pharmacogenetic studies.
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TLDR
This study corroborates previous findings indicating that knowledge of CYP2B6 genetic status should be taken into account for anEFV treatment and suggests that ABCB1 SNPs may also influence the clinical impact of EFV treatment.
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TLDR
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Although no genome-wide associations with virologic response to HAART overall were detected in this cohort of HIV-infected women, more statistically significant gene-level burden tests were observed than would be expected by chance and it is likely that variation in one of the significant genes is associated with virology response to certain HAART regimens.
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TLDR
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Population Pharmacokinetic/Pharmacogenetic Model for Optimization of Efavirenz Therapy in Caucasian HIV-Infected Patients
TLDR
The detailed genetic analysis conducted in this study identified two of 90 SNPs that significantly impacted CL/F, which might indicate that the remaining SNPs analyzed do not influence this PK parameter, at least in Caucasian populations with characteristics similar to those of the authors' study population.
Predictive Value of Known and Novel Alleles of CYP2B6 for Efavirenz Plasma Concentrations in HIV‐infected Individuals
TLDR
CYP2B6 poor metabolizer genotypes explain to a large extent EFV pharmacokinetics and identify individuals at risk of extremely elevated EFV plasma levels.
Efavirenz Pharmacokinetics in HIV-1-Infected Children Are Associated With CYP2B6-G516T Polymorphism
TLDR
CYP2B6-G516T polymorphisms significantly affect the CL/F rate of EFV in children and changes in hepatic enzyme activity by age may need to be considered when evaluating the impact of genetic variants on antiretroviral pharmacokinetics in children.
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