**Background:** Nearly a quarter of the world's population has latent TB infection (LTBI). Without antibiotics, approximately 5% of immunocompetent individuals progress to TB disease within two years of infection, with another 5% over their lifetime. This risk is higher for people living with HIV (PLWH). In lower TB incidence countries (<100 cases/100,000/year), screening and preventive treatment (PT) for LTBI among PLWH is often recommended, but guidelines on which groups to prioritise are contradictory and implementation is patchy. Evidence of cost-effectiveness may improve uptake and health outcomes at reasonable cost.
**Methods:** This systematic review assessed cost-effectiveness estimates of LTBI screening/PT strategies among PLWH in lower TB incidence countries. Databases (Ovid Embase, PubMed, Web of Science) were searched for articles published between 1 January 1980 and 30 September 2020. Studies had to include a health economic evaluation with a modelling component (decision tree, Markov, individual-based models) and report both health outcomes (e.g., QALYs gained, DALYs averted) and costs. Two reviewers independently screened papers at all levels. Data were extracted independently by two reviewers. Costs were inflation-adjusted to 2018 and converted to US$. Study reporting completeness was assessed using the CHEERS checklist, and study quality using the Gates Reference Case for Economic Evaluation.
**Key Results:** Of 2,644 articles screened, nine studies were included. Studies were from the US (3), UK (2), Italy (1), Japan (1), Brazil (1), and China/Hong Kong (1). All used dynamic-type Markov models except two (system dynamics model and individual-based transmission model). Cost-effectiveness estimates varied widely: universal screening/PT strategies from studies published in the past five years ranged from US$2,828 to US$144,929/QALY gained (2018 prices). Strategies targeting screening to higher-risk PLWH (e.g., those from high/medium TB incidence countries) were generally more cost-effective. For example, Capocci et al. 2020 found that screening all PLWH cost US$56,479–144,929/QALY, while targeted screening of PLWH from sub-Saharan Africa or middle TB incidence countries cost US$23,098–47,540/QALY. In the UK, BHIVA guidelines were more cost-effective than NICE guidelines (BHIVA: US$58,297/QALY; NICE 2016: US$131,643/QALY). Jo et al. 2021 reported highly favourable estimates for screening all PLWH in four US states: US$2,828/QALY (Florida) to US$11,265/QALY (New York). Key model inputs varied substantially: LTBI prevalence (5.3% to 55%), annual reactivation rates (2%/year to 39.1%/year), PT effectiveness (62% to 95%), and costs (full-course PT: US$103–1,333; active TB treatment: US$741–18,565). Only five studies included secondary TB transmission, and only one included HIV care/ART costs. Study quality varied (CHEERS scores 46–88%), with inconsistent reporting of methods and results limiting comparability.
**Clinical Implications:** The limited evidence suggests LTBI screening/PT may be cost-effective for some PLWH groups in lower TB incidence settings, particularly when targeted to those at higher risk (e.g., migrants from high TB incidence countries). However, the wide variation in cost-effectiveness estimates (US$2,828 to US$144,929/QALY) and the heterogeneity in study methods, assumptions, and target populations make it difficult for policymakers to draw firm conclusions. The review highlights the need for standardisation of model descriptions and results reporting, including systematic sensitivity analyses with Tornado plots and probabilistic sensitivity analysis with uncertainty ranges for ICER estimates. Further research is needed, particularly on strategies targeting screening/PT to PLWH at higher risk, and on cost-effectiveness for children living with HIV. As TB prevalence falls globally, targeting strategies will become increasingly important for maintaining cost-effectiveness while still contributing to TB elimination goals.