index
EDCTP portfolio: Tuberculosis
Facilitating implementation of TB testing
The TB-CAPT study will provide crucial information on the performance and impact of new TB diagnostics in real-life settings.
The challenge
Introduction of Xpert technology was a major step forward in the molecular diagnosis of TB as an alternative to culturing TB bacteria. However, although offering several significant advantages – notably, much faster results – its impact has been less than expected. This reflected some drawbacks in the Xpert technology, but also the fact that, in practice, clinicians do not rely solely on diagnostic test results when deciding on treatment.
As new generations of molecular diagnostic tests for TB become available, therefore, it will be important to consider not just their technical performance but also how they would contribute to clinical decision-making and working practices in existing healthcare systems.
The project
The TB-CAPT project is evaluating the impact of using the Truenat platform with the Truenat MTB-Plus assay for point-of-care diagnosis at the most peripheral level of health systems with limited infrastructure. The Truenat testing system uses portable, battery-operated devices to rapidly detect Mycobacterium tuberculosis complex bacteria (MTBC) and rifampicin resistance. The Truenat MTB Plus assay has recently been approved by WHO as a smear-replacement test.
Additionally, the TB-CAPT team assesses the impact of expanded drug-susceptibility testing using the Xpert XDR cartridges on patient-important outcomes such as time to results.
The consortium is evaluating the performance of these new tools at a range of sites in sub-Saharan Africa. One major aim of the project is to gather data on health outcomes and HIV-related mortality when new tools are used. But the study will also examine how the Truenat platform can improve care and logistical processes – from linking patients to care pathways to stock management.
It will also explore implications for staff training and practical matters such as stock management and maintenance, when the technology is used outside specialist laboratory facilities.
Impact
The TB-CAPT study will provide insight into the clinical benefits the Truenat platform might offer, based on its use in realistic contexts, and into the financial implications of its introduction. It will provide policymakers with much clearer evidence of the most impactful implementation strategies based on local patterns of disease and healthcare infrastructure, enabling them to make more informed decisions on the introduction of the new technology.
EDCTP portfolio: HIV & HIV-associated infections
The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.
Bringing antiretroviral drugs to children
“
crucial in
widening African
children’s access
to antiretrovirals
”
Introduction of Xpert technology was a major step forward in the molecular diagnosis of TB as an alternative to culturing TB bacteria. However, although offering several significant advantages – notably, much faster results – its impact has been less than expected. This reflected some drawbacks in the Xpert technology, but also the fact that, in practice, clinicians do not rely solely on diagnostic test results when deciding on treatment.
As new generations of molecular diagnostic tests for TB become available, therefore, it will be important to consider not just their technical performance but also how they would contribute to clinical decision-making and working practices in existing healthcare systems.
The challenge
The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.
The project
The TB-CAPT project is evaluating the impact of using the Truenat platform with the Truenat MTB-Plus assay for point-of-care diagnosis at the most peripheral level of health systems with limited infrastructure. The Truenat testing system uses portable, battery-operated devices to rapidly detect Mycobacterium tuberculosis complex bacteria (MTBC) and rifampicin resistance. The Truenat MTB Plus assay has recently been approved by WHO as a smear-replacement test.
Additionally, the TB-CAPT team assesses the impact of expanded drug-susceptibility testing using the Xpert XDR cartridges on patient-important outcomes such as time to results.
The consortium is evaluating the performance of these new tools at a range of sites in sub-Saharan Africa. One major aim of the project is to gather data on health outcomes and HIV-related mortality when new tools are used. But the study will also examine how the Truenat platform can improve care and logistical processes – from linking patients to care pathways to stock management.
It will also explore implications for staff training and practical matters such as stock management and maintenance, when the technology is used outside specialist laboratory facilities.
Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3
Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)
Target population(s): Children with HIV
Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)
Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)
Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)
EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)
Total project funding: €1.2M (CHAPAS-1); €5.0M
L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.
Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.
WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.
WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing
HIV infection: Recommendations for a public health approach
(second edition). 2016
Impact
ratios forfixed-dose combinations and on appropriatedosage according to weight.
The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.
The TB-CAPT study will provide insight into the clinical benefits the Truenat platform might offer, based on its use in realistic contexts, and into the financial implications of its introduction. It will provide policymakers with much clearer evidence of the most impactful implementation strategies based on local patterns of disease and healthcare infrastructure, enabling them to make more informed decisions on the introduction of the new technology.