Dr. Kesheng Wang Co-Authors Article on HIV Pharmacotherapy
Dr. Kesheng Wang, Associate Professor in the Department of Biostatistics and Epidemiology in the College of Public Health at East Tennessee State University, has co-authored a paper in the Clinical Drug Investigation. The article, “HIV Integrase Inhibitor Pharmacogenetics: An Exploratory Study,” presents an analysis of numerous genetic markers in relation to drug concentration changes, clinical outcomes, and the occurrence of subject-reported adverse events in human immunodeficiency virus (HIV) patients.
The study was led by Dr. Sam Harirforoosh of the Gatton College of Pharmacy. Dr. Derek E. Murrell, for whom this research served as a doctoral dissertation, is listed as the first author of this article. Other co-authors of this interdisciplinary project include Dr. David B. Cluck and Dr. Stacy D. Brown of the Gatton College of Pharmacy, and Dr. Jonathan P. Moorman and Dr. Michelle M. Duffourc of the Quillen College of Medicine.
After nearly four decades, HIV remains a high priority in biomedical research with thousands of new infections occurring each day, adding to the more than 36 million individuals worldwide who are living with HIV. Current drug treatments are highly effective in reducing plasma HIV viral load; however, several factors may interact to alter the efficacy and tolerability of antiretrovirals. 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.
In this study, the authors conducted an exploratory pharmacogenetic analysis of integrase strand transfer inhibitors regimens, consisting of numerous single nucleotide polymorphisms to investigate the influence of genetic polymorphism on drug concentrations (Ctrough), selected clinical parameters, and adverse event occurrence.
88 HIV patients were recruited for pharmacokinetic analysis. Eighty-six single nucleotide polymorphisms were polymorphic within this population and used for pharmacogenetic analysis. This exploratory study discovered several associations between variables and single nucleotide polymorphisms when using these regimens. Abnormal dream occurrence was statistically different between regimens. Additionally, several SNPs were found to be associated with adverse event profiles primarily when all regimens were grouped together.
“These results may show that pharmacogenetics may play some role in prediction of the adverse integrase inhibitor-based regimen outcomes;” state the authors. “These exploratory findings provide support for further examination of precision medicine in HIV pharmacotherapy.” In conclusion, the associations found in this study strengthen the need for further assessment within the HIV positive population of factors contributing to unfavorable subject outcomes.
This study was funded in part by a Research and Development Committee (RDC) Interdisciplinary Grant and a Graduate Studies Student Research Grant from East Tennessee State University.