Dolutegravir (DTG) and abacavir/lamivudine (ABC/3TC) generic dispersible tablets (DT) are recommended for use in young children with HIV. Pharmacokinetic (PK) data of these generic scored dispersible tablets administered once daily together are limited. This study aimed to describe PK data of DTG-DT with ABC/3TC-DT in young children weighing 6 to <20 kg in Thailand.
Children living with HIV weighing between 6 to <20 kg aged from 3 months to 7 years were eligible. DTG-DT (10 mg, Mylan Inc, VIARTIS[sup]TM[/sup]) and ABC/3TC-DT (120/60 mg, Mylan, VIARTIS[sup]TM[/sup])) were dosed using the following weight bands (WBs): 6-9.9 kg, 20/180/90 mg; 10-13.9 kg, 20/240/120 mg; and 14-<20 kg, 25/300/150 mg. Doses prescribed were in accordance with WHO recommendations, except for those in the 6-9.9 kg WB where DTG 20 mg rather than 15 mg was used. Pharmacokinetic studies were performed at steady-state (7-14 days after regimen initiation). Blood samples were collected at pre-dose and at 1, 2, 3, 4, 6, and 24 h post-dose. Results were compared with AUC[sub]0-24[/sub], CAUC[sub]24[/sub], C[sub]max[/sub] reported from the ODYSSEY trial (for DTG) and the ARROW study (for ABC/3TC). PK analyses were performed using Phoenix WinNonlin version 8.3 (Clinical trials registration: TCTR20201025001)
From 2 August 2021 to 3 October 2021, 18 children were enrolled with median age of 4.5 years (2.8-5.8) and 11 (61%) were male. Median (IQR) weight within each weight band were 9.4 kg (8.3-9.7), 12.8 kg (11.4-13.5), and 15.6 kg (15-19.9). Eleven were HIV RNA virologically suppressed and 7 viremic. DTG, ABC, and 3TC PK parameters are shown in Table 1. DTG AUC0-24, Cmax, and C 24values were generally higher than those reported in the ODYSSEY trial across all weight bands. DTG C 24 in WB 6-9.9 24 with 20 mg was closer to that observed in older children but highly variable. ABC/3TC for the 10-19.9 kg WB exposures trended higher compared with the ARROW study. There is no serious adverse event among all participants.
Generic DTG and ABC/3TC generic scored dispersible tablets provided adequate drug exposures in Thai children weighing 6 to <20 kg. DTG 20 mg in the lowest weight band produced higher drug exposure and C24. These initial data suggested that a DTG and ABC/3TC regimen with a slightly modified WHO weight band doses will be efficacious and safe for Thai children weighing <20 kg.