Krishna P Reddy1, Ankur Gupta-Wright2, Katherine L Fielding3, Sydney Costantini4, Amy Zheng5, Elizabeth L Corbett2, Liyang Yu4, Joep J van Oosterhout6, Stephen C Resch7, Douglas P Wilson8, C Robert Horsburgh9, Robin Wood10, Melanie Alufandika-Moyo11, Jurgens A Peters12, Kenneth A Freedberg13, Stephen D Lawn14, Rochelle P Walensky15. 1. Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: kpreddy@mgh.harvard.edu. 2. TB Centre, London School of Hygiene & Tropical Medicine, London, UK; Malawi-Liverpool-Wellcome Trust Clinical Research Program, Blantyre, Malawi. 3. TB Centre, London School of Hygiene & Tropical Medicine, London, UK; University of the Witwatersrand, Johannesburg, South Africa. 4. Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA. 5. Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. 6. Dignitas International, Zomba, Malawi; Department of Medicine, University of Malawi College of Medicine, Blantyre, Malawi. 7. Department of Health Policy and Management, Harvard T H Chan School of Public Health, Boston, MA, USA. 8. Department of Internal Medicine, Edendale Hospital, University of KwaZulu-Natal, Pietermaritzburg, South Africa. 9. Department of Epidemiology, Boston University School of Medicine, Boston, MA, USA; Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. 10. Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa. 11. Dignitas International, Zomba, Malawi. 12. TB Centre, London School of Hygiene & Tropical Medicine, London, UK. 13. Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Health Policy and Management, Harvard T H Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Boston University School of Medicine, Boston, MA, USA. 14. TB Centre, London School of Hygiene & Tropical Medicine, London, UK; Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa. 15. Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: UK Medical Research Council, UK Department for International Development, Wellcome Trust, US National Institutes of Health, Royal College of Physicians, Massachusetts General Hospital.
BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: UK Medical Research Council, UK Department for International Development, Wellcome Trust, US National Institutes of Health, Royal College of Physicians, Massachusetts General Hospital.
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