BackgroundPsychosocial challenges among human immunodeficiency virus (HIV)-positive patients may promote substance use disorders. This study explored the relationship between conjoint tobacco and alcohol use and depression symptoms among HIV positive patients in Sedibeng District, South Africa.MethodsIn a cross-sectional study of 404 participants, a questionnaire collected information on sociodemography, tobacco and alcohol use and depression symptoms. Outcome measures included the prevalence of conjoint tobacco and alcohol use and its association with positive screen for depression.ResultsThe mean participant age was 43.2 years. Most completed secondary school (62.9%), were black (99.0%), female (65.8%), unemployed (53.6%) and on antiretroviral therapy (ART) for > 1 year (97.8%). Current tobacco use was reported by 23.3% (n= 94) participants with most smoking cigarette (73.7%) and having low nicotine dependence (75.5%). Current alcohol use was reported by 43.6% (n= 176) participants, and 36.9% were categorised as harmful users. Only 7.7% (n= 31) participants screened positive for depression; the prevalence of conjoint tobacco and alcohol use was 19.6% (n= 79) and this was not associated with depression (p= 0.438). Harmful alcohol users were more than five times likely to report conjoint tobacco and alcohol use (p= 0.000), but women were less likely to report it (p= 0.000).ConclusionConjoint tobacco and alcohol use is common among patients with HIV infection. Although not associated with positive screen for depression, its relationship with harmful alcohol use reiterates the need for an integrated tobacco and alcohol use screening and treatment strategy in the HIV treatment programme in primary care.ContributionTo the authors best knowledge, this study is the first published study that explored the relationship between conjoint tobacco and alcohol use, and depression among HIV-positive patients in the South African primary care settings.