Background Tuberculosis (TB) incidence and mortality in people living with HIV can be reduced by TB preventive treatment (TPT). However, low levels of screening and uptake, poor adherence, and loss to follow-up considerably reduce its effectiveness. We therefore aimed to assess the losses within all steps of the screening and treatment cascade. Methods We carried out a comprehensive, global systematic review of the TPT cascade of care in people living with HIV (PROSPERO: CRD42020162396). To enhance data generalisability we included articles which reported the proportion of people living with HIV completing any step of the TPT cascade in low and high TB burden countries published before March 2024. Random effects meta-analysis produced pooled estimates of the proportion proceeding to the next step along the cascade. Results were explored through subgroup analyses and meta-regression. Results Data from 368 cohorts containing 2.7 million participants were included. High levels of heterogeneity in outcomes were seen. Most participants were from Africa (80.6%). Isoniazid monotherapy was used for TPT in 92.6% of cohorts, usually for 6 months. Substantial loss to follow-up was found throughout the treatment cascade, with more than one in six patients lost at the following steps: initial screening, immunological testing, treatment start and completion. Regimens lasting <6 months had higher completion rates (88.4%) than those lasting 6–9 months (74.4%) or>9 months (61.6%). Conclusions Our analysis highlights substantial loss to follow-up at multiple steps during the care cascade. This may significantly lower the reported effectiveness of TPT in real-world settings. Research and policy should focus on simplified care pathways and novel, shorter treatment regimens that optimise retention in care. © 2025 Elsevier B.V., All rights reserved. 6>