PhD (Health Sciences) / Department of Advanced Nursing Science / Background: Family-centred approaches to Prevention of Mother-to-Child Transmission (PMTCT) interventions present an important direction for sustainability and prevention of pediatric infections while improving overall family health. Despite numerous opportunities to sustain and expand the existing PMTCT interventions, Mother-to-Child Transmission (MTCT) still occurs. This is evidenced by the number of under-five children who are admitted in hospital being infected by the Human Immunodeficiency Virus (HIV) between the ages of 6 weeks to 18 months, whereas the Polymerase Chain Reaction (PCR) results was non-reactive at six weeks. Purpose: The purpose of this study was to develop a strategy to enhance family-centered interventions for PMTCT sustainability in the selected districts of Limpopo Province, South Africa. Phase 1: The study was conducted in phases. In Phase 1, which was empirical, the following objectives: to explore the risks that contribute to MTCT between the ages of 6 weeks and 18 months; to explore the perceptions of family members regarding family support in PMTCT interventions; and to explore the factors that affect the provision of family support in PMTCT interventions. Phase 2: was development of the strategy and validation of the strategy. Methods: The exploratory sequential mixed method was used to conduct the study, where qualitative data were collected and analyzed first; followed by collecting, analyzing and interpreting the quantitative data. The population comprised the following groups: mothers of babies between 6 weeks and 18 months who are living with HIV/AIDS, family members were represented by male partners, grandmothers or mother’s in_-law and health care professionals working at the PHC Heath Centers v or clinics rendering PMTCT services. In the qualitative design, participants were selected by non-probability purposive sampling and data were collected through one-to-one interview and focus group discussions. Data were analyzed utilizing the open-coding method. In the quantitative design, participants were selected by using simple random sampling and data were collected by means of self-administered survey questionnaires with structured close-and open-ended questions. The population were midwives from Capricorn, Mopani and Vhembe districts PHC clinic. Data were analyzed using the Statistical Package for the Social Sciences (SPSS), Version 22 and descriptive statistics. In Phase 2, findings from the data were used to develop an intervention strategy. The strategy was developed through the use of Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis. The developed strategy was validated by using a quantitative design. / NRF