Background
Current antiretroviral (ARV) syrups used for HIV prevention and early treatment in neonates are from older, more toxic drug classes. Dolutegravir (DTG) is one of the preferred ARVs for children, but there is no pediatric formulation specifically tailored for use in neonates. We report on the mothers’ acceptability of DTG dispersible tablets (DTG-DT) and a novel oral film (DTG-OF), not yet studied in children, in neonates enrolled in the PETITE-DTG study.
Methods
PETITE-DTG is an ongoing phase I/II, open-label 2-stage study evaluating the pharmacokinetics, safety and acceptability of 2 solid pediatric DTG formulations in term neonates in South Africa. In the multi-dose stage, 40 term neonates born to women receiving DTG are randomized to receive DTG-DT or DTG-OF with zidovudine (ZDV) syrup prophylaxis. The DTG-DT group receive 5 mg DTG-DT in 5mL water, administered with a syringe, followed by 2mL water from the same syringe. The DTG-OF group receive a single 5 mg dissolvable film from a sachet, folded and placed directly on the tongue. In-depth interviews were conducted in a sub-set of mothers at 3 time points and thematic analysis applied to determine acceptability.
Results
20 mother-infant pairs (10 neonates on DTG-DT and 10 on DTG-OF) were included in this analysis. Mothers reported very good acceptability to both DTG formulations. Mothers administering DTG-DT to their infants found that it dissolved easily, and was palatable (fruity smell, sweet) and appealing to babies. Challenges included technical and time-consuming preparation, and the large volume (7mL water) required. Mothers were concerned about spilling medicine and underdosing babies. For the DTG-OF, most mothers reported initial hesitancy and described the film as unfamiliar. Concerns included the inability of neonates to swallow the ‘paper’, but high levels of acceptance were reported after administering 1 to 2 doses, with DTG-OF preferred above ZDV. Convenient packaging (thin sachet), ease of administration (quick and easy to dissolve), and perceived dosing accuracy (no spilling) were reported with the film. Acceptability was further facilitated by reassurance from health workers that the ‘paper’ was indeed ‘medicine’.
Conclusions
Mothers reported acceptance of pediatric DTG formulations for use in neonates. After initial hesitancy, the DTG-OF was found to be highly acceptable by mothers. Targeted peer support and engagement with mothers and health workers will be important to familiarize end-users with the novel DTG-OF.
Table or Figure
