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BackgroundIn South Africa, traditional health practitioners’ (THPs) explanatory frameworks concerning illness aetiologies are much researched. However there is a gap in the literature on how THPs understand HIV-related opportunistic infections (OIs), i.e. tuberculosis, candidiasis and herpes zoster. This study aimed to comprehend THPs’ understandings of the aforementioned; to ascertain and better understand the treatment methods used by THPs for HIV and OIs, while also contributing to the documentation of South African medicinal plants for future conservation.MethodsThe study was conducted in two locations: Strand, Western Cape where THPs are trained and Mpoza village, Mount Frere, Eastern Cape from where medicinal plants are ordered or collected. Semi-structured interviews were conducted with 53 THPs of whom 36 were diviners (amagrirha: isangoma) and 17 herbalists (inyanga). THPs were selected through a non-probability “snowball” method. Data were analysed using a thematic content analysis approach. An ethnobotanical survey was conducted and plants used to manage HIV and OIs were collected. A complete set of voucher specimens was deposited at the University of the Western Cape Herbarium for identification. Plant names were checked and updated with Kew’s online website http://www.theplantlist.org.ResultsTHPs conceptualise the aetiology of HIV and OIs at two related levels. The first involves the immediate manifestation of the illness/condition because of a viral infection in the blood (HIV), the presence of bacteria in the lungs (tuberculosis), or weakened state of the body making it susceptible to OIs. The presence of OIs is indicative of the probable presence of HIV. The second level of causation affects the first, which includes pollution, changes in cultural sexual norms, witchcraft, environmental factors, and lack of adherence to ancestral rituals. THPs reported using 17 plants belonging to 12 families. Remedies included mixes of up to five plants.ConclusionThis study explored the THPs’ perspectives on HIV and commonly associated OIs and their herbal treatment methods. THPs generally rely on biomedical diagnosis before treating a client. They also seek guidance from the ancestors for a particular diagnosis, the plants to use for a specific treatment, when to harvest, and how to administer herbal remedies.Electronic supplementary materialThe online version of this article (doi:10.1186/1746-4269-10-77) contains supplementary material, which is available to authorized users.