e-Article
Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial.
Document Type
article
Author
Jacobs, Tom; Mumbiro, Vivian; Cassia, Uneisse; Zimba, Kevin; Nalwanga, Damalie; Ballesteros, Alvaro; Domínguez-Rodríguez, Sara; Tagarro, Alfredo; Madrid, Lola; Mutata, Constantine; Chitsamatanga, Moses; Bwakura-Dangarembizi, Mutsa; Passanduca, Alfeu; Buck, W; Nduna, Bwendo; Chabala, Chishala; Najjingo, Elizabeth; Musiime, Victor; Moraleda, Cinta; Colbers, Angela; Mujuru, Hilda; Rojo, Pablo; Burger, David
Source
Clinical Infectious Diseases. 78(3)
Subject
Language
Abstract
BACKGROUND: We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin. METHODS: Infants with HIV aged 1-12 months, weighing ≥3 kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD). Dolutegravir pharmacokinetic parameters, HIV viral load (VL) data, and adverse events (AEs) were reported. RESULTS: Twenty-seven of 30 enrolled infants had evaluable pharmacokinetic curves. The median (interquartile range) age was 7.1 months (6.1-9.9), weight was 6.3 kg (5.6-7.2), 21 (78%) received rifampicin, and 11 (41%) were female. Geometric mean ratios comparing dolutegravir BID with rifampicin versus OD without rifampicin were area under curve (AUC)0-24h 0.91 (95% confidence interval, .59-1.42), Ctrough 0.95 (0.57-1.59), Cmax 0.87 (0.57-1.33). One infant (5%) receiving rifampicin versus none without rifampicin had dolutegravir Ctrough