A range of studies have demonstrated that symptomatic hyperlactataemia and lactic acidosis are associated with antiretroviral combinations containing stavudine. Following a meta-analysis showing that lower doses of stavudine are safer and as effective, the World Health Organization (WHO) issued a statement that only a low dose of stavudine (30 mg) should be used. We performed a retrospective review of the records of 86 patients (aged 27 - 59 years) initiated on 30 mg or 40 mg stavudine-containing antiretroviral therapy regimens between 2004 and 2006 at the adult HIV clinic at Dr George Mukhari Hospital, Pretoria, South Africa. Our analysis demonstrated that stavudine dose reduction increased the odds of patients being more stable on treatment with fewer reported side-effects. Stavudine-containing regimens should be avoided in obese female patients. Low-dose stavudine (20 mg) may offer alternative solutions in poor or resource-limited settings, with a lower associated risk of toxicity and side-effects; however, virological non-inferiority to the first-line treatment option should be established.