Cost-Effectiveness Analysis of Xpert MTB/RIF Ultra for the Diagnosis of HIV-Associated Tuberculous Meningitis

BACKGROUND: Human immunodeficiency virus (HIV-1)-associated tuberculous meningitis (TBM) is the most lethal form of extrapulmonary tuberculosis, with a high mortality rate in sub-Saharan Africa. Due to the limited diagnostic performance of current testing, empiric treatment is frequently required as untreated TBM is almost universally fatal. Xpert MTB/RIF Ultra (Xpert Ultra) is the World Health Organization recommended first-line diagnostic test for TBM but is costly relative to the standard of care (SOC). We performed a cost-effectiveness analysis of Xpert Ultra for HIV-associated TBM in Zambia. METHODS: We developed a decision-analytic model comparing a diagnostic strategy guided by CSF Xpert Ultra plus the SOC (cerebrospinal fluid biochemistry and clinical suspicion) versus the SOC alone in adults with HIV and suspected TBM. Costs were calculated from a healthcare perspective, including medication, supplies, personnel, and overhead. The primary outcome was the incremental cost-effectiveness ratio in US dollars per quality-adjusted life-year gained. Sensitivity analyses and cost-effectiveness acceptability curves assessed robustness across a range of willingness-to-pay thresholds. RESULTS: Xpert Ultra plus the SOC was cost-effective, yielding an incremental cost-effectiveness ratio of $242.76 per quality-adjusted life-year gained. The number needed to test to prevent 1 TBM death was 125. Sensitivity analyses showed that cost-effectiveness was most influenced by TBM prevalence, the TBM mortality rate in treated patients, and the probability of empiric treatment. Xpert Ultra was approximately 88% likely to be cost-effective across a broad willingness-to-pay range. CONCLUSIONS: Xpert Ultra is cost-effective for diagnosing HIV-associated TBM in Zambia. These findings support World Health Organization guidelines recommending Xpert Ultra in high-burden, resource-limited settings.