“
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

Globally, 2 million children are living with HIV, 90% of them in sub-Saharan Africa. As access to antiretroviral therapy improves, more of these children are surviving to adolescence and adulthood.

One of the consequences of HIV infection is a shift in the balance between bone resorption and new bone formation, leading to loss of bone mass and bone weakening. Some HIV medications also lead to reduced bone mass. These effects are typically worse in young people from sub-Saharan Africa owing to high rates of past infections and malnutrition.

The VITALITY project aims to determine whether supplementation with vitamin D3 and calcium carbonate, key factors contributing to bone growth, can improve musculoskeletal health in young people aged 8–16 years with HIV infection. In addition, vitamin D supplementation may have beneficial effects on the immune system and on the development of healthy microbial communities in the gut (the microbiome).

This age group is critical, as puberty is the time when bone mass reaches its maximum (peak bone mass). During adulthood, bone mass gradually declines, so low peak bone mass increases vulnerability to bone fractures and conditions such as osteoporosis in later life.

The VITALITY project is conducting a randomised controlled trial of high-dose vitamin D3 and calcium carbonate supplementation in 800 children living with HIV in Zambia and Zimbabwe. Children will be treated for a year and followed for a further year. Although small trials of vitamin D supplementation have been run, the VITALITY study is the first large-scale trial to investigate this combination in sub-Saharan Africa.

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 VITALITY project will generate data on a simple, safe and affordable intervention that could have significant benefits for people living with HIV. Vitamin D3 has the potential to provide short-term benefits, with strengthened bones and the associated improvements in muscle mass helping to improve social participation and wellbeing. Over the longer term, greater peak bone mass in adolescence would reduce the risk of fractures and osteoporosis in adulthood and later life, safeguarding health and the risk of financial hardship due to loss of employment or treatment costs.

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