Fixed-dose combinations containing stavudine have played a critical role in the worldwide scale-up of antiretroviral therapy, but increasing concern exists regarding adverse events due to mitochondrial toxicity. We describe the first reported occurrence of lactic acidosis within a family of 3 HIV-infected individuals. This report is only the second of lactic acidosis affecting an African child. Further research is indicated to identify possible genetic and other risk factors underlying mitochondrial toxicity in African populations, especially among pediatric cohorts.