Information from the abstract
Background/Objectives: Despite its role as a first-line therapy for Thai people living with HIV (PLWH), dolutegravir (DTG) exhibits significant pharmacokinetic (PK) variability influenced by both genetic and non-genetic factors. This variability may contribute to an increased incidence of neuropsychiatric adverse events (NP-AEs) at the standard 50 mg once daily (OD) dose. Methods: To evaluate the impact of relevant covariates, a population PK model of DTG was developed using 1122 DTG plasma concentrations from 221 Thai PLWH. Monte Carlo simulations were performed to evaluate the probability of target attainment for pre-defined efficacy and safety thresholds across different dosage regimens. Results: Data were analyzed using a one-compartment model with first-order absorption incorporating lag-time, and first-order elimination. Body weight ( 95% of the population but resulted in a substantial proportion (30.46–85.68%) exceeding the safety threshold. In contrast, a reduced dose of 25 mg OD maintained high efficacy target attainment (>80%) while decreasing the proportion exceeding the safety threshold to
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Related topics: Pharmacogenetics and Drug Metabolism · HIV/AIDS drug development and treatment · HIV/AIDS Research and Interventions
Thai researcher and institutional participation
Anan Chanruang · Sasithorn Sirilun · Suthunya Chupradit · Sasiwimol Ubolyam · Napon Hiranburana · Anchalee Avihingsanon · Baralee Punyawudho · Chiang Mai University · HIV Netherlands Australia Thailand Research Collaboration · Chulalongkorn University
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