HIV Integrase Inhibitor Pharmacogenetics: An Exploratory Study

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.

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 < 0.05) association of selected clinical data with genetic variants within the study population.

In a sample (n = 88) with a median age of 52.5 years (IQR 45.7-57.2) being predominately Caucasian (88.6%) and male (86.4%), this exploratory study discovered several associations between variables and SNPs, when using INSTIs. Abnormal dream occurrence was statistically different (p = 0.028) between regimens. Additionally, several SNPs were found to be associated with adverse event profiles primarily when all regimens were grouped together.

The associations found in this study point to a need for further assessment, within the population living with HIV, of factors contributing to unfavorable subject outcomes. These exploratory findings require confirmation in larger studies, which then may investigate pharmacogenetic mechanisms.