Identification of Novel UGT1A1 Variants Including UGT1A1 454C>A through the Genotyping of Healthy Participants of the HPTN 077 Study.

ABSTRACT: Cabotegravir (CAB) is an integrase strand-transfer inhibitor of HIV that has proven effective for HIV treatment and prevention in a long-acting injectable formulation, typically preceded by an oral formulation lead-in phase. Previous in vitro studies have demonstrated that CAB is primarily metabolized via glucuronidation by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A9. In this study, we performed next-generation sequencing of genomic DNA isolated from the HPTN 077 participants to explore the variants within UGT1A1 and UGT1A9. Additionally, to enable correlation of UGT1A1 and UGT1A9 genotypes with plasma CAB-glucuronide levels, we quantified glucuronidated CAB following both oral administration of CAB and intramuscular injection of long-ac

SUBMITTER: Seneviratne HK 

PROVIDER: S-EPMC7888308 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature