OBJECTIVE: There are an estimated 38 million people with HIV (PWH), with significant economic consequences. We aimed to collate global lifetime costs for managing HIV. DESIGN: We conducted a systematic review (PROSPERO: CRD42020184490) using five databases from 1999 to 2019. METHODS: Studies were included if they reported primary data on lifetime costs for PWH. Two reviewers independently assessed the titles and abstracts, and data were extracted from full texts: lifetime cost, year of currency, country of currency, discount rate, time horizon, perspective, method used to estimate cost and cost items included. Descriptive statistics were used to summarize the discounted lifetime costs [2019 United States dollars (USD)]. RESULTS: Of the 505 studies found, 260 full texts were examined and 75 included. Fifty (67%) studies were from high-income, 22 (29%) from middle-income and three (4%) from low-income countries. Of the 65 studies, which reported study perspective, 45 (69%) were healthcare provider and the remainder were societal. The median lifetime costs for managing HIV differed according to: country income level: $5221 [interquartile range (IQR)]: 2978-11 177) for low-income to $377 820 (IQR: 260 176-541 430) for high-income; study perspective: $189 230 (IQR: 14 794-424 069) for healthcare provider, to $508 804 (IQR: 174 781-812 418) for societal; and decision model: $190 255 (IQR: 13 588-429 772) for Markov cohort, to $283 905 (IQR: 10 558-453 779) for microsimulation models. CONCLUSION: Estimating the lifetime costs of managing HIV is useful for budgetary planning and to ensure HIV management is affordable for all. Furthermore, HIV prevention strategies need to be strengthened to avert these high costs of managing HIV.