Cost-effectiveness of novel algorithms for rapid diagnosis of tuberculosis in HIV-infected individuals in Uganda

Abstract

Objective: Xpert MTB/RIF ('Xpert') and urinary lateral-flow lipoarabinomannan (LF-LAM) assays offer rapid tuberculosis (TB) diagnosis. This study evaluated the cost-effectiveness of novel diagnostic algorithms utilizing combinations of Xpert and LF-LAM for the detection of active TB among people living with HIV.

Design: Cost-effectiveness analysis using data from a comparative study of LF-LAM and Xpert, with a target population of HIV-infected individuals with signs/symptoms of TB in Uganda.

Methods: A decision-analysis model compared multiple strategies for rapid TB diagnosis:sputum smear-microscopy; sputum Xpert; smear-microscopy combined with LF-LAM; and Xpert combined with LF-LAM. Primary outcomes were the costs and DALY's averted for each algorithm. Cost-effectiveness was represented using incremental cost-effectiveness ratios (ICER).

Results: Compared with an algorithm of Xpert testing alone, the combination of Xpert with LF-LAM was considered highly cost-effective (ICER $57/DALY-averted) at a willingness to pay threshold of Ugandan GDP per capita. Addition of urine LF-LAM testing to smear-microscopy was a less effective strategy than Xpert replacement of smear-microscopy, but was less costly and also considered highly cost-effective (ICER $33 per DALY-averted) compared with continued usage of smear-microscopy alone. Cost-effectiveness of the Xpert plus LF-LAM algorithm was most influenced by HIV/ART costs and life-expectancy of patients after TB treatment.

Conclusion: The addition of urinary LF-LAM to TB diagnostic algorithms for HIV-infected individuals is highly cost-effective compared with usage of either sputum smear-microscopy or Xpert alone.

Fig. 1. Schematic of algorithm utilizing smear-microscopy alone versus algorithm utilizing Xpert with LF-LAM

Schematic diagram of decision analysis model for TB diagnostic algorithms with and without Xpert and/or LF-LAM. Not all branches are shown. Schematic for algorithm 2 (Smear/LF-LAM) and algorithm 3 (Xpert alone) are shown in Supplemental content 1. *Individuals are eligible to return to clinic/hospital for repeat evaluation, with incremental increases in diagnosis. We assumed increased TB treatment mortality for individuals with delayed diagnoses (Supplemental Content for additional model and parameters). DALYs, disability-adjusted life years; DST, drug sensitivity testing.

Fig. 2. Cost-effectiveness acceptability curves inclusive of all health system costs including HIV and ART costs

Compared with the Reference ‘Smear’ algorithm, at WTP threshold of GDP per capita ($487) per DALY-averted, ‘Smear/LF-LAM’ was cost-effective in 72% of simulations, ‘Xpert’ was cost-effective in 60% of simulations, ‘Xpert/LF-LAM’ was cost-effective in 64% of simulations. All algorithms were cost-effective in 100% of simulations if the WTP threshold of three times GDP per capita per DALY averted is used. Compared to ‘Xpert’ algorithm, ‘Xpert/LF-LAM’ was cost-effective in 77% of simulations at WTP of $487/DALY-averted, and 100% of simulations at WTP thresholds above three times GDP per capita per DALY averted. When HIV/ART care costs are excluded, all rapid diagnostic algorithms were considered cost-effective in 100% of simulations.