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This thesis assesses the uptake of the national Prevention of Mother to Child Transmission of HIV (PMTCT) programme in South Africa, and the challenges of achieving safe infant feeding practices in the context of HIV. The research studies contained in this thesis utilised a variety of quantitative and qualitative research methods in order to provide a full understanding of the challenges of moving from efficacy to effectiveness in PMTCT programmes. The first paper utilised a cross-sectional approach to a programme evaluation, papers two and three utilised qualitative methodologies, and paper four was based on a longitudinal cohort study design. The findings highlight the low uptake of PMTCT interventions and inappropriate infant feeding choices. The experiences of women with HIV provide an important insight into the difficulties of operationalising the WHO/UNICEF HIV and infant feeding recommendations in real life settings, where rates of HIV disclosure are low and mixed feeding is the norm. Several personal and environmental characteristics were identified that contributed to success in maintaining exclusive infant feeding practices. The research provides some guidance on the definition of appropriateness in infant feeding choices, and highlights the poor outcomes associated with formula feeding under unsafe conditions. Modifying infant feeding practices is essential in order to reduce postnatal HIV transmission and improve child survival. Interventions to improve infant feeding need to include improving the quality of counselling and support provided by health workers, with more structured assessments used to guide infant feeding choices. Efforts are also needed at the community level to increase rates of disclosure and to promote exclusive infant feeding as a norm.