“
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

Type 2 diabetes is a growing challenge in sub-Saharan Africa. Almost 20 million people in the region are currently affected, with numbers projected to rise to nearly 50 million by 2045. Even more alarmingly, an estimated 45 million people have early signs of diabetes – a number that could rise to 110 million by 2045. Even though many of those affected are unaware of their condition, treatment costs already amount to US$9.5 BN a year.

There is now substantial evidence that metformin, an affordable drug widely used to treat diabetes, is also effective at preventing the development of diabetes in those at increased risk of the condition (such as those with pre-diabetes, increased blood glucose levels). Its use is highly cost-effective. However, metformin remains underutilised for diabetes prevention and its effectiveness has not been assessed in all populations, such as those living with HIV. 

The META TRIAL team is already running a phase II trial in Tanzania assessing the impact of metformin on diabetes prevention in people living with HIV who are on antiretroviral therapy and have been diagnosed with pre-diabetes. This follow-on project will take advantage of the infrastructure established in Tanzania in order to organise a larger phase III study in the same target population.

The project aims to recruit 2,000 patients on antiretroviral therapy – making it the largest trial of its kind in Africa. Patients will be followed for three years and, as well as progression to diabetes, data will be gathered on financial impacts, health-related quality of life and cost-effectiveness.

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.

Antiretroviral therapy is becoming more widely available – 14 million people in the region are currently receiving antiretroviral therapy. With improved survival, increasing numbers of people in the region will be living to ages at which the risk of non-communicable diseases such as diabetes begins to increase sharply. Furthermore, there is evidence that HIV-infected individuals are at higher risk of diabetes. Without action, these conditions will have a major impact on the health, quality of life and financial wellbeing of households and countries. Increasingly, care for people with HIV will therefore need to encompass prevention and treatment of co-morbidities such as diabetes.

Data from the META TRIAL study will reveal whether metformin is an effective drug for diabetes prevention in people living with HIV, as well as its likely cost-effectiveness – evidence that will be of global as well as regional importance.

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