“
crucial in

widening African

children’s access

to antiretrovirals

”

Bringing antiretroviral drugs to children

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

The challenge

The BCG (Bacillus Calmette-Guérin) vaccine has been used to vaccinate against TB since the 1920s. It is reasonably effective at preventing serious disease, but many vaccinated infants still develop TB meningitis and it appears to have little impact on the spread of pulmonary TB. Modelling studies suggest that, despite BCG, around 7.5 million children were infected with Mycobacterium tuberculosis in 2010 and 650,000 developed TB disease.

BCG is a weakened or attenuated version of Mycobacterium bovis, a relative of M. tuberculosis that causes TB in cattle. Researchers have recently revisited M. bovis and introduced precise genetic changes that cause it to stimulate stronger immune responses and make it safer for use in individuals with HIV, who sometimes suffer reactions to conventional BCG.

The large-scale phase III priMe study will build on promising preliminary trials, in adults and children, of this updated version of BCG, known as VPM1002. Aiming to recruit around 7000 newborns, it will provide definitive evidence of the safety and efficacy of VPM1002 in both HIV-free and HIV-infected newborn infants.

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.

Positive findings would indicate that VPM1002 is a suitable alternative to BCG, widely recognised to be an imperfect vaccine but included in most countries’ routine immunisation programmes; it would also provide a suitable vaccine for infants with HIV. Furthermore, production methods for VPM1002 are relatively simple and straightforward to scale up, so the vaccine could meet global demand and overcome some of the supply difficulties recently experienced with BCG. The priMe study will also generate important data on the immune responses associated with good protection against M. tuberculosis, to enhance the design of future vaccines.

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