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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

More than 10 million people developed TB in 2015, and 2 million people died of TB disease. People living with HIV are at greatly increased risk of TB disease: HIV co-infection increases the risk of TB disease by up to 30 times.

Notably, only one in 10 people with a Mycobacterium tuberculosis (Mtb) infection develop TB disease, suggesting that the immune system can usually contain infections. However, factors such as HIV infection compromise the body’s ability to keep Mtb under control.

Professor Wendy Burgers has developed an extensive programme of research on the impact of HIV infection on the immune system. As well as HIV vaccine development, her work also has important implications for HIV–TB co-infections.

TB is increasingly seen as encompassing a spectrum from quiescent infection through to active disease. It would be highly advantageous to know who was at risk of progressing to active disease, but development of biomarkers to identify such individuals is held back by a lack of understanding of the drivers of disease. As HIV infection tilts the scales in favour of active disease, studying HIV–TB co-infections may reveal critical disruptions that drive TB disease. 

In her EDCTP Senior Fellowship, Professor Burgers is focusing on a class of immune cells called Th22 cells, which produce the cytokine interleukin-22 (IL-22). The numbers of Th22 cells are greatly reduced in HIV infections, and there is some evidence that IL-22 plays a protective role in respiratory infections.

To shed more light on their possible role in TB, Professor Burgers is carrying out a detailed investigation of Th22 cell responses during TB disease and treatment, after HIV infection and during antiretroviral therapy. Th22 cell responses in these different disease states will be compared with those of other immune cell populations potentially involved in 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.

Professor Burgers’ Senior Fellowship project will provide key data on Th22 responses, with potential implications for vaccine design and the development of biomarkers predictive of disease progression. The project will also support the clinical research training of two PhD students, one master’s student and a postdoctoral fellow, building research capacity in this critical area.

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