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Background: Antiretroviral therapy (ART) roll-out is fraught with challenges, many with serious repercussions. We explored and described patient behaviour-related challenges from the perspective of health care providers from non-governmental organisations involved in ART programmes in KwaZulu-Natal, South Africa. Methods: A descriptive case study design using qualitative approach was applied during this study. Data was collected from nine key informants from the three biggest NGOs involved in ART roll-out using in-depth semistructured interviews. Transcribing and coding for emergent themes was done by two independent reviewers. Ethical approval for the study was granted by the UNISA research ethics committee of The Faculty of Health Sciences. Written consent was obtained from directors of the three NGOs involved and individual audio taped informed consent was obtained from all study participants prior to data collection. Results: Findings revealed six broad areas of patient behaviour challenges. These were patient behaviour related to socio-economic situation of patient (skipping of medication due to lack of food, or due to lack of transport fees), belief systems (traditional and religious), stigma (non- disclosure), sexual practices (non-acceptability of condoms, teenage pregnancies), escapism (drug and alcohol abuse) and opportunism (skipping medication in order to access disability grant, teenage pregnancies in order to access child grant). Conclusion: New programmes need to address patient behaviour as a complex phenomenon requiring a multipronged approach that also addresses social norms and institutions. In the face of continued ART scale up, this is further evidence for the need for multi-sectoral collaboration to ensure successful and sustainable ART roll-out. [ABSTRACT FROM AUTHOR]