Determining the perceived acceptability of an intervention designed to improve health literacy around developmentally appropriate play during infancy, with a community advisory group of mothers, in Soweto, South Africa.

Children require opportunities to participate in unstructured, unrestricted active play as infants, to encourage positive health, socioemotional and developmental outcomes in life. Certain social and environmental factors in the home setting can limit participation in play, particularly in low resource settings. As caregivers are their infants' first teachers, they have the important role of providing opportunities and space for children to learn through play. This mixed methods, cross-sectional study aimed to test the acceptability of an intervention developed to improve health literacy around play and development with mothers from Soweto, South Africa. Fifteen mothers with infants aged 0-3 months were included to form a Community Advisory Group (CAG). Two rounds of focus group discussions (FGDs) were conducted to explore the understanding of, and barriers to play and development, and to determine the acceptability of an intervention prototype. The prototype included developmentally appropriate activities presented in video format, demonstrations of how to make toys, infographics and other educational material which would be delivered to participants as part of the intervention. A further questionnaire was administered to participants one week after the FGD to determine the acceptability of intervention activities which the participants completed at home, with their infants. Participants reported several barriers to play, including limited options for safe outdoor play, overcrowding, insufficient time, limited resources, and conflicting information. Participants suggested that the intervention content be delivered every 1-2 weeks, through a data-free app. Overall, the prototype activities tested at home were deemed acceptable. The reported barriers, together with reduced motivation and self-efficacy observed in the participants, guided the researchers to develop intervention content focused on improving health literacy in play and development, delivered in the form of an interactive mobile app. Future research will develop and test the efficacy of this intervention in a low resource setting in South Africa.

Protocol for the PLAY Study: a randomised controlled trial of an intervention to improve infant development by encouraging maternal self-efficacy using behavioural feedback.

INTRODUCTION: The early infant caregiving environment is crucial in the formation of parent-child relationships, neurobehavioural development and thus child outcomes. This protocol describes the Play Love And You (PLAY) Study, a phase 1 trial of an intervention designed to promote infant development through encouraging maternal self-efficacy using behavioural feedback, and supportive interventions. METHODS AND ANALYSIS: 210 mother-infant pairs will be recruited at delivery from community clinics in Soweto, South Africa, and individually randomised (1:1) into two groups. The trial will consist of a standard of care arm and an intervention arm. The intervention will start at birth and end at 12 months, and outcome assessments will be made when the infants are 0, 6 and 12 months of age. The intervention will be delivered by community health helpers using an app with resource material, telephone calls, in person visits and behavioural feedback with individualised support. Every 4 months, mothers in the intervention group will receive rapid feedback via the app and in person on their infant's movement behaviours and on their interaction styles with their infant. At recruitment, and again at 4 months, mothers will be screened for mental health risk and women who score in the high-risk category will receive an individual counselling session from a licensed psychologist, followed by referral and continued support as necessary. The primary outcome is efficacy of the intervention in improving maternal self-efficacy, and the secondary outcomes are infant development at 12 months, and feasibility and acceptability of each component of the intervention. ETHICS AND DISSEMINATION: The PLAY Study has received ethical approval from the Human Research Ethics Committee of the University of the Witwatersrand (M220217). Participants will be provided with an information sheet and required to provide written consent prior to being enrolled. Study results will be shared via publication in peer-reviewed journals, conference presentation and media engagement. TRIAL REGISTRATION NUMBER: This trial was registered with the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za) on 10 February 2022 (identifier: PACTR202202747620052).

72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study.

BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. INTERPRETATION: Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing. FUNDING: Unitaid.