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

BACKGROUND: HIV-associated tuberculous meningitis (TBM) is the most lethal form of extrapulmonary tuberculosis, with high mortality 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 (WHO) recommended first line diagnostic test for TBM but is costly relative to standard of care. 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 standard of care (CSF biochemistry and clinical suspicion) versus standard of care 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 (ICER) in US dollars per quality-adjusted life-year (QALY) gained. Sensitivity analyses and cost-effectiveness acceptability curves (CEAC) assessed robustness across a range of willingness-to-pay (WTP) thresholds. RESULTS: Xpert Ultra plus standard of care was cost-effective yielding an ICER of $242.76 per QALY gained. The number needed to test to prevent one TBM death was 125. Sensitivity analyses showed cost-effectiveness was most influenced by TBM prevalence, TBM mortality in treated patients, and the probability of empiric treatment. Xpert Ultra was approximately 88% likely to be cost-effective across a broad WTP range. CONCLUSIONS: Xpert Ultra is cost-effective for diagnosing HIV-associated TBM in Zambia. These findings support WHO guidelines recommending Xpert Ultra in high-burden, resource-limited settings.