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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

Despite some progress, HIV/AIDS remains a huge disease burden in sub-Saharan Africa. In South Africa alone, 7.5 million people are living with HIV and 200,000 new infections occur each year.

Intriguingly, a small number of people – known as HIV controllers – seem naturally able to repress HIV replication even without antiretroviral drugs. In so-called ‘elite controllers’, virus replication is undetectable. Less positively, HIV controllers are at increased risk of a range of health complications, particularly inflammatory conditions, as are people on antiretroviral therapy, even if they are controlling HIV replication.

In her Senior Fellowship, Dr Christina Thobakgale is investigating the role of the innate immune response in HIV control and vulnerability to HIV-associated complications. The innate immune response is an early, non-specific defence response, and there is growing interest in its contribution to control of HIV.

Dr Thobakgale will be analysing the properties of different types of innate immune cell from HIV controllers and elite controllers, comparing them to those from people showing more typical responses to HIV infection.

For example, she will be investigating particular types of dendritic cell, which can orchestrate more powerful immune responses to HIV, and natural killer cells, which destroy virus-infected cells. She will also be exploring the properties of monocytes, white blood cells that can also be infected by HIV, which may act as a reservoir of virus and could also contribute to the vulnerability to complications. A particular focus will be on cell metabolism and energy production by mitochondria, which may be altered by HIV infection.

The Senior Fellowship builds on Dr Thobakgale’s past work on the innate immune system and HIV infection, particularly the role of natural killer cells and HIV mutations that enable the virus to evade host responses. In recognition of her promising early research, the South African Ministry of Science and Technology named her runner up in its distinguished young women in science award and she has been nominated to join the Academy of Science of South Africa and the African Academy of Science.

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 Thobakgale’s studies are addressing a health problem of particular relevance in South Africa. Her findings will provide insight into the elements of the innate immune response important to HIV control, and those linked to inflammatory complications. The results will have important implications for both the treatment and potential prevention of HIV infections, as well as for minimising the risk of inflammatory complications.

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