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

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Bringing antiretroviral drugs to children

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

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