Publications

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

Prof. Keertan Dheda

South Africa

EDCTP portfolio: Senior Fellowships

Professor Keertan Dheda is building the capacity of African researchers to apply genomics and other new technologies in the battle against TB.

Applying new technologies in TB research

An estimated 2.5 million people fall ill with TB in sub-Saharan Africa every year, with more than 400,000 deaths. These figures include 1 million new infections in children and 250,000 deaths.

The challenges of TB are being exacerbated by the emergence of multidrug-resistant TB and extensively drug-resistant TB, which require long periods of hospitalisation and treatment.

The challenge

Professor Keertan Dheda is one of Africa’s leading authorities on TB. He is Head of the Division of Pulmonology at the University of Cape Town, having built up a large research group from scratch. His group’s work has a strong focus on developing improved services for local populations in the Western Cape, and in South Africa and Africa more generally. He has pioneered the adoption of new techniques into clinical practice, and developed research programmes in all areas of TB diagnosis, treatment and care. He has led several successful EDCTP-funded projects on TB diagnostics, and was awarded the 2018 EDCTP Scientific Leadership Prize.

In his EDCTP Senior Fellowship, Professor Dheda aims to further develop his own leadership capabilities, and build local capacity in new genomics and other ‘omics’ technologies. This will include setting up a genome sequencing platform to support the training of early-career researchers in a technology increasingly central to infectious disease research. 

His fellowship will build on a trial being funded by the South African Medical Research Council, NExT RCT, led by Professor Dheda, which is evaluating a new six-month needle-free regimen for multidrug-resistant TB. Biobanked samples will be used in a range of projects. One study is evaluating biomarkers potentially associated with response to TB treatment – current trials are long and costly because no good markers currently exist that predict treatment responses. A second study will use next-generation genome sequencing to identify resistance mutations. A third study will investigate methods to enable genome sequence information to be derived directly from clinical samples.

The project

Professor Dheda’s Senior Fellowship will enable him to undertake professional development activities so he can extend his leadership role in the African and global TB research community. In addition, it will support the introduction of new technologies that will accelerate research on diagnosis and treatment of this critical disease, and facilitate the training of junior researchers (a postdoctoral fellow and a PhD student).

Impact


test the safety and efficacy of this new formulation in young children

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

An estimated 2.5 million people fall ill with TB in sub-Saharan Africa every year, with more than 400,000 deaths. These figures include 1 million new infections in children and 250,000 deaths.

The challenges of TB are being exacerbated by the emergence of multidrug-resistant TB and extensively drug-resistant TB, which require long periods of hospitalisation and treatment.

Professor Keertan Dheda is one of Africa’s leading authorities on TB. He is Head of the Division of Pulmonology at the University of Cape Town, having built up a large research group from scratch. His group’s work has a strong focus on developing improved services for local populations in the Western Cape, and in South Africa and Africa more generally. He has pioneered the adoption of new techniques into clinical practice, and developed research programmes in all areas of TB diagnosis, treatment and care. He has led several successful EDCTP-funded projects on TB diagnostics, and was awarded the 2018 EDCTP Scientific Leadership Prize.

In his EDCTP Senior Fellowship, Professor Dheda aims to further develop his own leadership capabilities, and build local capacity in new genomics and other ‘omics’ technologies. This will include setting up a genome sequencing platform to support the training of early-career researchers in a technology increasingly central to infectious disease research. 

His fellowship will build on a trial being funded by the South African Medical Research Council, NExT RCT, led by Professor Dheda, which is evaluating a new six-month needle-free regimen for multidrug-resistant TB. Biobanked samples will be used in a range of projects. One study is evaluating biomarkers potentially associated with response to TB treatment – current trials are long and costly because no good markers currently exist that predict treatment responses. A second study will use next-generation genome sequencing to identify resistance mutations. A third study will investigate methods to enable genome sequence information to be derived directly from clinical samples.

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.

Professor Dheda’s Senior Fellowship will enable him to undertake professional development activities so he can extend his leadership role in the African and global TB research community. In addition, it will support the introduction of new technologies that will accelerate research on diagnosis and treatment of this critical disease, and facilitate the training of junior researchers (a postdoctoral fellow and a PhD student).

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