Infectious Disease · Medical Literature
Acceptability of a Dolutegravir Oral Dispersible Film in Term Neonates Born to Mothers Living With HIV.
Abstract
Dolutegravir (DTG) is a key antiretroviral (ARV) drug for children living with HIV, but no specific formulation is available for neonates (<28 days old). One of the DTG formulations evaluated in the PETITE-DTG trial was a novel 5 mg oral DTG dispersible film (DTG-Film). Acceptability to end-users is essential when introducing new ARV drugs. We report on the experiences of mothers and health workers related to the DTG-Film. PETITE-DTG was a phase I/II, open-label two-stage study evaluating the pharmacokinetics, safety and acceptability of two paediatric DTG formulations in term neonates in South Africa. In the multi-dose stage, 43 term neonates born to women with HIV were randomized to receive either the 5 mg DTG-Film or half of a 10 mg DTG dispersible tablet, in addition to zidovudine syrup prophylaxis, for 28 days. In-depth interviews were conducted in a sub-set of mothers whose neonates received DTG-Film (at three time points) and with health workers (at two time points). Thematic analysis was employed. Data were collected (September 2023-October 2024) from 16 virologically suppressed mothers (median age: 38 years) whose neonates received DTG-Film and six female health workers (median age: 47 years) involved in the study. Usability was described positively-with participants highlighting ease of administration, quick dissolution, accurate dosing with no spillage and convenient packaging. Some mothers were initially hesitant due to unfamiliarity with the film, but after 1-2 doses, most reported liking or preferring the DTG-Film above other known ARV formulations. The film integrated well into households, was supported by family members and was considered discreet, helping to avoid unintentional HIV-status disclosure. Previous experience with neonatal ARV drugs and trust in health workers supported acceptability. Health workers noted DTG-Film was potentially fit for use in public health settings, where other formulations require manipulation prior to administration. Health workers played a key role in reassuring mothers that the "paper" was indeed medicine. Mothers and health workers found the new DTG-Film acceptable for neonatal use. While initial hesitancy was noted, acceptability increased with use. Targeted peer support and engagement with mothers and health workers will be essential to familiarize end-users with the novel DTG-Film.
Clinical relevance
Is a novel 5 mg dolutegravir oral dispersible film (DTG-Film) acceptable to mothers and health workers when administered to term neonates born to women living with HIV as part of a prophylaxis regimen? __SNAPSHOT__ {"studyDesign":"Qualitative sub-study (thematic analysis of in-depth interviews) nested within PETITE-DTG, a Phase I/II, open-label, single-centre, two-stage randomized trial","setting":"Tygerberg Hospital, South Africa (single-centre); data collected September 2023 – October 2024","sampleSize":"Qualitative sub-study: n=22 (16 mothers whose neonates received DTG-Film + 6 female health workers). Parent RCT multi-dose stage: n=43 neonates randomized (DTG-Film arm: n=20; DTG dispersible tablet arm: n=21, per Lancet HIV companion publication)","population":"Term neonates (≥37 weeks gestational age, birthweight ≥2 kg) born to virologically suppressed women living with HIV on dolutegravir-based ART; mothers had a median age of 38 years. Neonates were at low risk of HIV acquisition given maternal viral suppression.","intervention":"5 mg dolutegravir oral dispersible film (DTG-Film): a taste-masked, mint-flavoured, thin hydrophilic polymeric film (15 × 25 mm) placed on the neonatal tongue, administered every 48 hours for the first 2 weeks of life, then daily through 28 days, in addition to standard zidovudine syrup prophylaxis","comparator":"For the acceptability sub-study: no formal comparator (qualitative design). For the parent RCT: half of a scored 10 mg DTG dispersible tablet (yielding 5 mg dose), same dosing schedule","primaryOutcome":"Acceptability of the DTG-Film to end-users (mothers and health workers), assessed via in-depth interviews analysed by thematic analysis; no quantitative primary endpoint defined for this qualitative sub-study","followUp":"Mothers interviewed at three time points over 28 days of neonatal DTG-Film administration; health workers interviewed at two time points over the same period","fundingSource":"Not reported in the provided abstract; the parent PETITE-DTG trial (NCT05590325) has been conducted in South Africa — funding source not explicitly stated in available sources"}
Key findings
This qualitative sub-study reported that initial hesitancy toward the DTG-Film among both mothers and health workers was followed by increased acceptability with use over the 28-day neonatal prophylaxis period. The DTG-Film, described as a small, thin (15 × 25 mm), mint-flavoured, rapidly dissolving formulation placed on the infant's tongue, was preferred by mothers over the dispersible tablet in part because it reduced the risk of dose spillage and ensured more complete drug delivery compared to tablet-based administration requiring water and a cup or syringe. Qualitative themes related to ease of administration and dose certainty emerged as key drivers of acceptability. No quantitative acceptability metrics, response rates, or comparative statistics between formulations are reported in the available abstract. In the parent PETITE-DTG trial (Lancet HIV, 2025), both formulations met pre-specified pharmacokinetic targets (geometric mean Ctrough >0.67 µg/mL; individual Cmax <17.0 µg/mL), no adverse events were attributable to dolutegravir, and the highest severity adverse events observed were two grade 3 events (pneumonia) in a single neonate unrelated to the study drug — these safety data provide important clinical context for the acceptability findings reported here but are from a companion publication, not this JIAS sub-study.
Practice implications
This study established that the 5 mg DTG-Film was acceptable to both mothers and health workers in a South African tertiary setting, with acceptability improving over the course of the 28-day neonatal prophylaxis course despite initial hesitancy. The findings support the feasibility of implementing a DTG-Film–based neonatal dosing strategy as an alternative to dispersible tablet administration. The study did not establish superiority of the DTG-Film over the dispersible tablet in adherence, clinical outcomes, or pharmacokinetics — these were assessed in the companion Lancet HIV publication. The findings apply specifically to virologically suppressed mothers and their term, healthy-weight neonates at low risk of HIV acquisition in a well-resourced research setting in South Africa; generalizability to higher-risk neonates (e.g., those born to mothers with detectable viral loads), preterm infants, lower-resourced community settings, or other countries is not established. Health workers were all female and numbered only six, limiting representativeness. As this is a qualitative study with a small purposive sample, statistical inference is not applicable and selection bias cannot be excluded. The DTG-Film has received tentative FDA approval for PEPFAR programmes but is not yet commercially available or incorporated into national programmes, meaning real-world implementation data are absent. Practice change is not yet warranted based on acceptability data alone; confirmatory implementation research in broader settings and regulatory approval of neonatal dosing labelling are needed. Only the abstract was available for this JIAS sub-study; additional qualitative themes and methodological detail (e.g., saturation, reflexivity, member-checking) cannot be assessed. __LIMITATIONS__ Very small qualitative sample (16 mothers, 6 health workers) drawn from a single research site, limiting transferability,All health worker informants were female; perspectives of male clinicians and community health workers not captured,Single-centre study at a tertiary academic hospital in South Africa — may not reflect community-level or lower-resource settings where most neonatal HIV prophylaxis occurs,Purposive sampling of mothers whose neonates specifically received DTG-Film introduces selection bias; experiences of families in the comparator arm not reported in this sub-study,Qualitative thematic analysis is inherently subjective; information on coding reliability, analyst triangulation, or member-checking is not available from the abstract,No quantitative acceptability metrics reported, preventing comparison with thresholds used in other ARV acceptability studies,Neonates were at low risk of HIV acquisition (virologically suppressed mothers), limiting applicability to higher-transmission-risk scenarios where DTG-Film may also be needed for treatment,DTG-Film is not yet commercially available or part of any national neonatal HIV programme, meaning findings reflect a controlled trial context,Only the abstract was available for detailed review; full qualitative data, theme saturation, and supplementary analyses could not be assessed,Funding source not reported — potential conflicts of interest cannot be evaluated __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ The 5 mg dolutegravir oral dispersible film demonstrated growing acceptability among mothers and health workers over a 28-day neonatal prophylaxis course in a South African tertiary setting, with ease of administration and reduced spillage risk cited as key advantages over dispersible tablets. These qualitative findings, combined with pharmacokinetic and safety data from the companion PETITE-DTG trial, support the formulation's feasibility for neonatal use, but the DTG-Film is not yet commercially available and implementation outside of trial conditions has not been evaluated. Confirmatory acceptability data from community settings, regulatory approval of neonatal labelling, and procurement pathways are required before this formulation can be recommended for routine clinical practice.