Dolutegravir population pharmacokinetics in racially, sex‐ and age‐diverse and antiretroviral therapy‐experienced adults with <scp>HIV</scp> in the United States

OBJECTIVES: Dolutegravir (DTG) has been associated with weight gain in women with HIV, Black people with HIV and people with HIV60 years. This study aimed to characterise DTG population pharmacokinetics (PopPK) in a diverse population including these sub-populations. METHODS: We conducted an intensive PK study nested within the Multicenter AIDS Cohort Study (MACS)/Women's Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS) and retrospectively quantified DTG plasma concentrations in historical specimens from participants in the WIHS and the MACS over several study visits. PopPK models were developed using NONMEM; covariate searches included relevant demographics and co-medications. RESULTS: The analysis included 44 people with HIV from the MWCCS (56.8% women, 72.7% Black, 40.9% 60 years), 193 WIHS women (52.8% Black, 25.4% 60 years) and 137 MACS men (19.7% Black, 53.3% 60 years). A one-compartment model with first-order absorption and elimination and an absorption lag time (ALAG) best described DTG PK. Apparent clearance (CL/F) was 1.21, 1.26 and 0.95 L/h; apparent volume of distribution (V/F) was 21.2, 38.9 and 19.8 L, in the MWCCS, WIHS and MACS, respectively. For all three models, ALAG was 0.35 h. Sex, race and age were not statistically significant covariates. In the WIHS, lower total bilirubin and current cigarette smoking were significantly associated with higher CL/F, and higher body weight was significantly associated with higher V/F. CONCLUSIONS: Our analysis did not support different DTG PK in women with HIV, Black people with HIV and people with HIV aged 60 years compared to other sub-populations; causal analysis between DTG concentrations and weight gain over time are ongoing.