Publications

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

Dr Catherine Riou

South Africa

EDCTP portfolio: Senior Fellowships

Dr Catherine Riou is aiming to identify cellular markers characteristic of different stages of TB disease.

Immunological signatures of TB infection

In 2017, TB was responsible for an estimated 1.7 million deaths; more than a quarter of TB deaths occur in Africa.

Most people who are infected with Mycobacterium tuberculosis (Mtb) do not develop active disease. However, it is becoming clear that the traditional distinction between active and latent or quiescent TB is too simplistic. Instead, there is likely to be a spectrum of disease states, with people at differing risks of progressing to severe disease.

The challenge

Dr Catherine Riou is aiming to identify specific immune system markers that are able to differentiate different TB disease states. Her focus is on T cells, specifically the CD4+ class of T cells. She and her colleagues have shown that the properties of CD4+ T cells differ between latent and active TB, in both HIV-infected and -uninfected patients. Furthermore, levels of a specific class of Mtb-specific CD4+ T cells expressing the CD153 marker are significantly higher in people with latent TB compared with those with active disease, and these cells are known to confer protection against TB in mice.

In her EDCTP Senior Fellowship, Dr Riou is studying in more detail the characteristics of T cell populations in different TB disease states. In particular, she is exploring whether people at heightened risk of active TB – with HIV infections or early signs of TB disease – show changes in the properties of Mtb-specific CD4+ T cells. In addition, she will test whether these changes are reversed by prophylactic TB treatment or antiretroviral therapy, which are known to reduce the risk of active TB disease.

The project

Dr Riou’s Senior Fellowship project will improve understanding of a critical aspect of the immune response to Mtb infection. It also has the potential to identify specific markers that could detect those at greatest risk of developing active TB and be used to monitor responses to therapy. The project will also build capacity by contributing to the training of two PhD students and a postdoctoral scientist.

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

In 2017, TB was responsible for an estimated 1.7 million deaths; more than a quarter of TB deaths occur in Africa.

Most people who are infected with Mycobacterium tuberculosis (Mtb) do not develop active disease. However, it is becoming clear that the traditional distinction between active and latent or quiescent TB is too simplistic. Instead, there is likely to be a spectrum of disease states, with people at differing risks of progressing to severe disease.

Dr Catherine Riou is aiming to identify specific immune system markers that are able to differentiate different TB disease states. Her focus is on T cells, specifically the CD4+ class of T cells. She and her colleagues have shown that the properties of CD4+ T cells differ between latent and active TB, in both HIV-infected and -uninfected patients. Furthermore, levels of a specific class of Mtb-specific CD4+ T cells expressing the CD153 marker are significantly higher in people with latent TB compared with those with active disease, and these cells are known to confer protection against TB in mice.

In her EDCTP Senior Fellowship, Dr Riou is studying in more detail the characteristics of T cell populations in different TB disease states. In particular, she is exploring whether people at heightened risk of active TB – with HIV infections or early signs of TB disease – show changes in the properties of Mtb-specific CD4+ T cells. In addition, she will test whether these changes are reversed by prophylactic TB treatment or antiretroviral therapy, which are known to reduce the risk of active TB disease.

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.

Dr Riou’s Senior Fellowship project will improve understanding of a critical aspect of the immune response to Mtb infection. It also has the potential to identify specific markers that could detect those at greatest risk of developing active TB and be used to monitor responses to therapy. The project will also build capacity by contributing to the training of two PhD students and a postdoctoral scientist.

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