“
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

An estimated 60 million people in sub-Saharan Africa are infected with hepatitis B virus (HBV), which can lead to long-term liver damage and potentially fatal cancer. Many people face the dual risk of HBV and malaria, and co-infections are common.

Both HBV and the malaria parasite infect liver cells, and it is possible that infections with one pathogen may influence immune responses to the other. HBV infections could also impair immune responses to malaria vaccines, but as HBV-infected people are excluded from malaria vaccine trials this is not known for certain.

Dr Kwado Kusi has carried out a series of studies examining immune responses to malaria, including responses that might have the potential to be used as markers of recent infection. His studies have also identified responses associated with protection against malaria, highlighting possible antigens to include in malaria vaccines.

In his Senior Fellowship, Dr Kusi aims to find out more about the impact of HBV infection on immune responses against the liver stage of the malaria parasite. More specifically, he will test the idea that chronic HBV infections have a generalised inhibitory effect on immune responses, dampening down the responses required to protect against malaria liver-stage infections. 

In his project, Dr Kusi is recruiting people in Accra, Ghana, with chronic HBV infections and following them monthly for a year. He will measure antibody levels against a sporozoite protein, to provide a measure of Plasmodium infection, as well as levels of asexual blood-stage parasites, an indication of how well the parasite has survived the liver stage of infection.

He will also gather data on liver function and HBV viral load to provide an indication of how a malaria infection affects HBV and liver disease.

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 Kusi’s work will fill a key evidence gap, shedding light on the impact of HBV and malaria parasite co-infections on immune responses. The findings will have important implications for the treatment of people with HBV who contract malaria. In addition, as malaria vaccines move closer to routine use, the results will help to determine how effective a vaccine is likely to be in populations with high levels of HBV infection.

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