Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

The CAP-TB study will provide crucial information on the performance and impact of new TB diagnostics in real-life settings.

Facilitating implementation of TB testing

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 CAP-TB project is examining practical implementation issues for an updated version of Xpert, known as Cepheid Omni. The Omni platform enables high sensitivity testing for TB (Omni/Ultra) and detection of a greater range of drug resistance genes (Omni/XDR).

The CAP-TB team is evaluating the performance of these new tools at a range of sites in sub-Saharan Africa. One aim of the project is to gather data on health outcomes and HIV-related mortality when the new tools are used. But the study will also examine how Omni technology, including its internet connectivity, 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.

The project

The CAP-TB study will provide insight into the clinical benefits the Omni 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 introduction of the new technology.

Impact


crucial in

widening African

children’s access

to antiretrovirals

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

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 CAP-TB project is examining practical implementation issues for an updated version of Xpert, known as Cepheid Omni. The Omni platform enables high sensitivity testing for TB (Omni/Ultra) and detection of a greater range of drug resistance genes (Omni/XDR).

The CAP-TB team is evaluating the performance of these new tools at a range of sites in sub-Saharan Africa. One aim of the project is to gather data on health outcomes and HIV-related mortality when the new tools are used. But the study will also examine how Omni technology, including its internet connectivity, 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.

The project

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 CAP-TB study will provide insight into the clinical benefits the Omni 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 introduction of the new technology.

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.

Impact

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

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