Screening all hospitalised patients with HIV for tuberculosis (TB) using urine tests would improve life expectancy and be cost-effective in Malawi and South Africa, according to research. TB is the leading killer of people with HIV worldwide. Many cases are missed by standard testing strategies that rely on sputum, as some patients are too unwell to provide a sputum specimen. A urine specimen, on the other hand, can be obtained from nearly all patients.
Led by the London School of Hygiene & Tropical Medicine (LSHTM) and Massachusetts General Hospital, the study was carried out alongside the STAMP Trial. The STAMP Trial demonstrated that using urine tests to screen for TB among HIV-positive patients, rather than sputum tests, could improve patient outcomes and reduce mortality from TB. In this additional study researchers wanted to further examine the clinical outcomes of urine testing for TB among HIV-positive patients in Malawi and South Africa, along with the economic impacts.
Using a computer simulation model of HIV and TB, researchers matched short-term clinical outcomes reported by the STAMP Trial and projected longer-term outcomes, such as financial implications of implementing urine testing.
The team found that screening all hospitalised patients with HIV for TB using a urine-based ‘dipstick’ test (called TB-LAM) could increase life expectancy by 0.5 to 1.2 years, and be cost-effective compared to sputum testing alone.
As in the STAMP Trial, both sputum and urine tests were used to screen participants, with urine testing found to be particularly effective for increasing TB diagnoses and reducing deaths, with a cost of only $3 per test.
Ankur Gupta-Wright, co-author from LSHTM, said: “Compared to other diagnostic strategies, urine testing is relatively easy and inexpensive and can detect cases of TB that would have otherwise been missed. Using urine tests to screen for TB among HIV-positive patients, some extremely unwell, can provide a result in under 30 minutes and be done at the patient’s bedside.”
Until now it had not been clear whether urine testing of all hospitalised patients with HIV would be useful and offer good value. With initial results showing that urine testing was cost-effective, the team them examined the financial implications of implementing urine TB screening among all hospitalised patients with HIV in Malawi and South Africa.
Combining both the costs of urine tests and costs of finding and treating more TB cases, researchers found that over five years the urine screening strategy would increase health care costs for these patients by $37m (10.8%) in Malawi and $261m (2.8%) in South Africa.
Krishna Reddy, lead author from Massachusetts General Hospital, said: “Urine testing for TB saves lives and is an efficient use of resources. Our findings have huge implications for increasing the survival of people with HIV in Africa and in other places where TB is common. Because patients live longer, health care costs increase, but the impact is modest – it’s a wise investment.”
The World Health Organisation currently recommends the use of urine LAM in selected patients only.
The authors say that the results of both the STAMP Trial and this cost-effectiveness analysis provide evidence for expanding the use of urine LAM testing to all hospitalised patients with HIV, regardless of symptoms or suspicion of TB, in areas where HIV and TB are common.
The research team acknowledge the limitations of their study, including that the true prevalence of active TB might differ from the estimates used in the study. However, sensitivity analyses showed that the intervention of urine testing would remain cost-effective across a wide range of TB prevalence.
The study was funded by the UK Medical Research Council, the UK Department for International Development, Wellcome Trust, US National Institutes of Health, the Royal College of Physicians and 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.
Krishna P Reddy, Ankur Gupta-Wright, Katherine L Fielding, Sydney Costantini, Amy Zheng, Elizabeth L Corbett, Liyang Yu, Joep J van Oosterhout, Stephen C Resch, Douglas P Wilson, C Robert Horsburgh Jr, Robin Wood, Melanie Alufandika-Moyo, Jurgens A Peters, Kenneth A Freedberg, Stephen D Lawn, Rochelle P Walensky