Thesis (M.CUR.) --University of Limpopo, 2014. / Background: The national HAART programme in South Africa was launched in April 2004. Highly Active Antiretroviral Therapy (HAART) is the medication that slows down the progression from HIV to AIDS, while it had been introduced in Western countries in 1996. Adherence to ART is the major factor in ensuring the virologic success of an initial regimen and is a significant determinant of survival for HIV-infected patients with the wild type virus who are on highly active antiretroviral treatment. Patients with suboptimal adherence are at risk, not only of HIV progression but also of the development of drug resistance and consequent narrowing of options for future treatment. Sub-Saharan Africa carries the highest burden of HIV infections and HIV / AIDS related mortality in the world. South Africa is reported to have the largest population living with the HIV infection. Aims: The aim of the study was to explore factors that contributed to non- adherence of patients to HAART at the Kanyamazane Clinic, Ehlanzeni District, Mpumalanga Province. Study method: A qualitative, exploratory, descriptive, and contextual research design was used for this study. A non-probability purposive sampling method was used to select participants ranging from 15 to 60 years of age and who were on HAART for more than one year. Fifteen participants were selected and the sample size was determined by data saturation. Semi-structured interviews were conducted to collect data through the use of an interview guide on their structured follow-up dates and audio recordings of the interviews were made. Data was analysed following the Tesch’s method. Themes and sub-themes were developed. Results: Findings indicate that factors contributing to non-adherence of patients to HAART are the patient-provider relationship and delivery of services, waiting hours and overcrowding, working hours of the facility, forgetfulness and experiencing better health, belief systems, side-effects, pill burden, migration due to employment, poverty and unemployment, as well as disclosure, stigma, and discrimination. Conclusion and recommendations: The study recommends that HAART services should be provided every day, including on weekends, to improve access and to reduce waiting times; and economic empowerment through skills acquisition programmes to participants and provision of jobs to earn a living. Keywords: Non-adherence, highly active antiretroviral treatment, regimen, drug resistance.