HIV Integrase Inhibitor Pharmacogenetics: An Exploratory Study

Background and Objectives Integrase strand transfer inhibitors (INSTIs), dolutegravir, elvitegravir, and raltegravir, have become integral in the treatment of HIV, with close monitoring of continued efficacy and tolerability. As side effect occurrence varies among subjects receiving these drugs, we...

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Veröffentlicht in:Clinical drug investigation 2019-03, Vol.39 (3), p.285-299
Hauptverfasser: Murrell, Derek E., Cluck, David B., Moorman, Jonathan P., Brown, Stacy D., Wang, Ke-Sheng, Duffourc, Michelle M., Harirforoosh, Sam
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Sprache:eng
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Zusammenfassung:Background and Objectives Integrase strand transfer inhibitors (INSTIs), dolutegravir, elvitegravir, and raltegravir, have become integral in the treatment of HIV, with close monitoring of continued efficacy and tolerability. As side effect occurrence varies among subjects receiving these drugs, we sought to perform an exploratory analysis examining the role of several single-nucleotide polymorphisms (SNPs) on drug concentration changes, selected clinical outcomes, and the occurrence of subject-reported adverse events. Methods Adults (aged ≥ 18 years) receiving INSTI-based regimens for treatment of HIV were recruited and genotyped with an iPLEX ADME PGx Pro v1.0 Panel. Multiple linear or logistic regression with covariates [age, sex, BMI, regimen (in the across-regimen group), regimen duration, and baseline variables (for continuous parameters)] was used to detect significant ( p  
ISSN:1173-2563
1179-1918
DOI:10.1007/s40261-018-0739-9