ObjectivesAfrican potato (hypoxis hemerocallidea) is used against HIV to enhance immune-function, although no studies have evaluated its use in HIV infected individuals on combination antiretroviral therapy. The study aimed to evaluate the acute effects of orally administered hypoxoside, a constituent of African potato, on the hepatic and renal function in HIV infected individuals on tenofovir disoproxil fumarate/ lamivudine/ efavirenz regimen. MethodsThis was an open-label, two-period, fixed-sequence, pre-post test study, pilot design. Ethical approval was obtained from Medical Research Council of Zimbabwe (MRCZ A/2045) and Medicines Control Authority of Zimbabwe (MCAZ CT134/2016). Blood samples were collected before and after administration of African potato tablets. Tablets were administered orally once daily at 15 mg/ kg hypoxoside for 10 days. Hepatic function tests (ALT, AST, ALP, GGT, albumin, total/ direct bilirubin); renal function tests (eGFR, blood urea nitrogen, creatinine), serum electrolytes (sodium, potassium, chloride) were assayed. STATA was used for statistical analysis. ResultsTwenty-six participants were enrolled (85 % female). Median age (range) was 43 (28–52) years. Most had overweight Body Mass Index (46 %) and were married (54 %). No statistical difference was noted during hypoxoside for AST/ ALT/ ALP/ GGT/ albumin/ bilirubin. There were no changes in creatinine/ eGFR/ electrolytes. A mean significant increase in total protein (p = 0.04) and decrease in blood urea nitrogen (p = 0.04) were noted. ConclusionShort-term exposure to hypoxoside from African potato appeared safe and was not associated with clinically significant changes in hepatic, renal function tests/ electrolytes. There is further need to evaluate extent of systemic exposure during long-term use in a larger population. Clinical trial registration numberPACTR201909691101062