Cost-effectiveness of urine-based tuberculosis screening in hospitalised patients with HIV in Africa: a microsimulation modelling study.

Krishna P Reddy,Stephen C Resch,Sydney Costantini,Stephen D Lawn,Katherine L Fielding,Amy Zheng,Robin Wood,Douglas P Wilson,C Robert Horsburgh,Ankur Gupta-Wright,Joep J Van Oosterhout,Jurgens A Peters,Liyang Yu,Rochelle P Walensky,Elizabeth L Corbett,Melanie Alufandika-Moyo,Kenneth A Freedberg

doi:10.1016/s2214-109x(18)30436-4

Abstract

Testing urine improves the number of tuberculosis diagnoses made among patients in hospital with HIV. In conjunction with the two-country randomised Rapid Urine-based Screening for Tuberculosis to Reduce AIDS-related Mortality in Hospitalised Patients in Africa (STAMP) trial, we used a microsimulation model to estimate the effects on clinical outcomes and the cost-effectiveness of adding urine-based tuberculosis screening to sputum screening for hospitalised patients with HIV. We compared two tuberculosis screening strategies used irrespective of symptoms among hospitalised patients with HIV in Malawi and South Africa: a GeneXpert assay (Cepheid, Sunnyvale, CA, USA) for Mycobacterium tuberculosis and rifampicin resistance (Xpert) in sputum samples (standard of care) versus sputum Xpert combined with a lateral flow assay for M tuberculosis lipoarabinomannan in urine (Determine TB-LAM Ag test, Abbott, Waltham, MA, USA [formerly Alere]; TB-LAM) and concentrated urine Xpert (intervention). A cohort of simulated patients was modelled using selected characteristics of participants, tuberculosis diagnostic yields, and use of hospital resources in the STAMP trial. We calibrated 2-month model outputs to the STAMP trial results and projected clinical and economic outcomes at 2 years, 5 years, and over a lifetime. We judged the intervention to be cost-effective if the incremental cost-effectiveness ratio (ICER) was less than US$750/year of life saved (YLS) in Malawi and $940/YLS in South Africa. A modified intervention of adding only TB-LAM to the standard of care was also evaluated. We did a budget impact analysis of countrywide implementation of the intervention. The intervention increased life expectancy by 0·5-1·2 years and was cost-effective, with an ICER of $450/YLS in Malawi and $840/YLS in South Africa. The ICERs decreased over time. At lifetime horizon, the intervention remained cost-effective under nearly all modelled assumptions. The modified intervention was at least as cost-effective as the intervention (ICERs $420/YLS in Malawi and $810/YLS in South Africa). Over 5 years, the intervention would save around 51 000 years of life in Malawi and around 171 000 years of life in South Africa. Health-care expenditure for screened individuals was estimated to increase by $37 million (10·8%) and $261 million (2·8%), respectively. Urine-based tuberculosis screening of all hospitalised patients with HIV could increase life expectancy and be cost-effective in resource-limited settings. Urine TB-LAM is especially attractive because of high incremental diagnostic yield and low additional cost compared with sputum Xpert, making a compelling case for expanding its use to all hospitalised patients with HIV in areas with high HIV burden and endemic tuberculosis. UK Medical Research Council, UK Department for International Development, Wellcome Trust, US National Institutes of Health, Royal College of Physicians, Massachusetts General Hospital.

Highlights

Tuberculosis is the leading cause of death among the 25 million people with HIV in sub-Saharan Africa.[1]
Testing urine with a lateral flow assay for Mycobacterium tuberculosis lipoarabinomannan (Determine TB-LAM Ag test, Abbott, Waltham, MA, USA [ formerly Alere]; TB-LAM) or with the GeneXpert assay for M tuberculosis and rifampicin resistance (Cepheid, Sunnyvale, CA, USA; Xpert) increases tuberculosis diagnostic yield in hospitalised patients with HIV.[4,5,6]
Testing urine with the GeneXpert assay for Mycobacterium tuberculosis and rifampicin resistance (Cepheid, Sunnyvale, CA, USA; Xpert) and TB-LAM increases diagnostic yield in people with HIV, those with very low CD4 cell counts, symptoms suggestive of tuberculosis, or both

Summary

Introduction

Tuberculosis is the leading cause of death among the 25 million people with HIV in sub-Saharan Africa.[1]. We identified two cost-effectiveness analyses, published before the Rapid Urine-based Screening for Tuberculosis to Reduce AIDS-related Mortality in Hospitalised Patients in Africa (STAMP) randomised trial and another multicountry randomised trial of TB-LAM in hospitalised patients with HIV were completed. Testing urine with the GeneXpert assay for Mycobacterium tuberculosis and rifampicin resistance (Cepheid, Sunnyvale, CA, USA; Xpert) and TB-LAM increases diagnostic yield in people with HIV, those with very low CD4 cell counts, symptoms suggestive of tuberculosis, or both. Model-based studies have shown that addition of urine TB-LAM testing to standard tuberculosis diagnostic strategies in people with HIV with low CD4 cell counts and symptoms of tuberculosis is cost-effective. The STAMP trial assessed the clinical benefit of urine tuberculosis screening in unselected hospitalised patients with HIV, regardless of CD4 cell count, tuberculosis symptoms, or suspicion of tuberculosis. We have used modelling to critically weigh long-term clinical benefits against costs

Methods

Results

Conclusion