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Magister Curationis - MCur / Depression is defined as a psychiatric condition, wherein a person experiences extreme sadness, social withdrawal, and expresses self-deprecating thoughts. Across the world, millions of people with Human Infectious Virus (HIV) suffer from depression each year. Depression is regarded as the most common disabling medical condition that affects both HIV-positive and HIV-negative individuals, globally. It is further reported that depression is the most common neuropsychiatric disturbance observed in HIV infected individuals. In South Africa, the prevalence of depression symptoms among Antiretroviral Therapy (ART) clients is reported to be 25.4%. However, depression among this group is often underdiagnosed and untreated in Primary Health Care settings. The need for routine screening is encouraged by studies confirming that depression and anxiety disorders accelerate the progression of HIV disease. Methods A quantitative descriptive research design was used. The study population included 1 440 males and females, aged eighteen years and over, who were HIV positive and received ART at the Clinic. A randomly selected sample of 372 respondents were recruited, but 110 had to be excluded because of eligibility issues; therefore, 262 respondents completed the Beck Depression Inventory (BDI) questionnaire. Mann-Whitney U test, Fisher’s exact test and the Spearman Rank test were used to analyse the data, using GraphPad Prism software. Depression symptoms were evaluated, using BDI, and a score of -> 10 indicated depression. Results Of the 262 respondents, 52% had club membership, compared to 48%, who were only on ART. There were significantly more female respondents (44%) involved in Adherence Clubs, as opposed to their male counterparts (8%), a difference of 36% overall (p=0.016). In summary, the number of individuals, who were suffering from some form of depression, enrolled in ART Adherence Clubs was 8.4% of the total sample, compared to 10% of those who were not in ART adherence clubs. The overall prevalence of depression in this current study was 18.4 %, which was in line with other studies conducted in a South African context, and a similar setting. Clinical depression status represents the main outcome of interest in this research project. The model category was 0-10, which indicated that a significant majority, 69.5%, n= 182, of the enrolled respondents were classified as healthy, in terms of clinical depression status. Beck depression scores were consistent across gender. Depression seemed to be more severe in the 35-44 age category. Fisher’s exact test confirmed the absence of any statistical difference between ART club membership and their depression status. Spearman rank correlation coefficient of -0.02 indicates a very low association between length of HIV seropositivity and Beck Depression score. Conclusion This is the first study reporting on the prevalence of depression, in relation to HIV infection, as well as ART treatment, and the associated adherence programme in Cape Town. Further research on a similar topic is recommended, using other instruments in the same geographic area.