Cost-effectiveness of Targeted Next-Generation Sequencing for Tuberculosis Drug-resistance Testing as an Alternative to the Standard of Care in South Africa

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BACKGROUND: South Africa faces emerging resistance to tuberculosis drugs like bedaquiline. Phenotypic drug-susceptibility testing (DST), the current reference standard for bedaquiline DST, has long turnaround times. Targeted next-generation sequencing (tNGS) offers a comprehensive alternative, potentially delivering faster results. However, these advantages must be weighed against differences in cost and test accuracy. METHODS: We used a decision tree model to evaluate the cost-effectiveness of tNGS against the standard of care (SOC) in South Africa across different levels of tNGS decentralization. Key outcomes included survival rates, time to a correct resistance profile, infectious time, and disability-adjusted life years (DALYs). Sensitivity analyses assessed the impact of drug-resistance prevalence, tNGS sensitivity, and improved DST access on overall cost-effectiveness. RESULTS: tNGS averted 408 DALYs and correctly identified 90.7% of resistance profiles as compared to 87.7% with SOC. Based on model assumptions for South Africa, tNGS had a reduced turnaround time and averted 97 years of infectious time. Centralized tNGS was cost-saving relative to SOC; however, decentralization of tNGS resulted in higher costs per DALY averted ($671-$2454). tNGS performance, relative to the SOC, improved at higher bedaquiline resistance and with increased sensitivity. Any increase in DST access through tNGS would improve cost-effectiveness in decentralized scenarios. CONCLUSIONS: tNGS could be cost-saving (centralized) or cost-effective (decentralized) in South Africa and has the potential to improve patient outcomes by returning a greater number of correct results in a shorter time. This analysis should be replicated across other settings to evaluate the broader feasibility of tNGS for DST.