HIV Integrase Inhibitor Pharmacogenetics and Clinical Outcomes: An Exploratory Association Study

• Main Author: Murrell, Derek E
• Format: Others
• Language: English
• Published: Digital Commons @ East Tennessee State University 2018
• Subjects: Dolutegravir; Elvitegravir; Raltegravir; Pharmacogenetics; HIV; Adverse events; Other Pharmacy and Pharmaceutical Sciences; Pharmacology; Virus Diseases
• Online Access: https://dc.etsu.edu/etd/3465; https://dc.etsu.edu/cgi/viewcontent.cgi?article=4926&context=etd

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years old) receiving an INSTI regimen were recruited (n=88). Subject genotypes were evaluated using an iPLEX PGx Panel. Genetic variations within our population, underwent multiple regression with covariates [age, sex, BMI, regimen duration, and baseline variables (as required) along with specific regimen in the comprehensive group] to detect significant (p=0.028) between abnormal dream occurrence and specific INSTI regimen with the raltegravir grouping presenting a higher frequency. This exploratory study also discovered several SNP-outcome associations when using INSTIs. Although these SNPs were found to have a role in predicting segments of adverse effect profiles, the clinical significance of these findings remains to be determined. Larger studies will be needed to confirm these exploratory findings with functional studies to understand pathogeneses. In conclusion, the associations found in this study strengthen the need for further assessment, within the HIV+ population, of factors contributing to unfavorable subject outcomes.