552. Evaluation of Relationships Between UGT1A1 Genotypes and Cabotegravir Long-Acting Injection Pharmacokinetics Among HIV-Infected Subjects in the LATTE-2 Study

摘要

BackgroundCabotegravir (CAB), an HIV integrase inhibitor primarily metabolized by UGT1A1, is in development as an oral tablet and long-acting (LA) intramuscular (IM) injection for the treatment and prevention of HIV infection. CAB LA has a prolonged absorption phase, typical of flip-flop PK, which yields prolonged drug exposure compared with oral administration. Genetic variation in UGT1A1 affects enzymatic activity, impacting drug exposure. A previous analysis in healthy and HIV-infected subjects demonstrated that UGT1A1 genotypes conferring poor metabolizer status were significantly associated with steady-state oral CAB PK parameters, with ~1.5-, 1.4-, and 1.3-fold increases in mean Cτ, AUC, and Cmax, respectively, in subjects with low vs. normal genetically predicted UGT1A1 activity. These increases are not considered clinically relevant. This analysis evaluated the impact of UGT1A1 genotypes on CAB PK in subjects who received both oral CAB and CAB LA in the LATTE-2 study.