“
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.

The challenge

Group B streptococci are carried by a third of adults and one in five pregnant women, in the digestive system or lower vaginal tract. They usually cause no problems, but they can be transmitted to babies in the womb or during birth. Because of their immature immune systems, babies are at greater risk of invasive disease such as meningitis and septicaemia, and group B streptococci can also cause stillbirth.

There are an estimated 410,000 cases of serious infection each year, leading to 147,000 stillbirths and infant deaths globally. The highest burden is in Africa, which accounts for 64% of stillbirths and infant deaths.

The PREPARE study aims to facilitate the development of vaccines against group B streptococci. Although serious – one in ten babies with an infection are likely to die, and half of those who survive meningitis will have long-term impairments – it is relatively rare, so large-scale phase III trials are difficult to conduct.

The PREPARE study is partnering with manufacturers to test two experimental vaccines, in women with and without HIV. To facilitate trials, the project will collect data on group B streptococcal infections and pregnancy outcomes in 70,000 women attending a hospital in Uganda. A biobank of blood samples will also be created, so links between antibody production and protection against group B streptococci-associated disease in mothers and babies can be investigated. 

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.

The PREPARE study will generate important data on the efficacy of experimental vaccines against group B streptococci, but will also provide additional evidence on disease burden in sub-Saharan Africa and on the immune responses linked to protection. A deeper understanding of the latter could provide a more convenient way to assess the efficacy of vaccines, to inform licensing decision-making and accelerate the introduction of a vaccine.

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