Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

EDCTP portfolio: Malaria

The ASAAP study is evaluating a novel triple combination to protect current antimalarial drugs and to provide an alternative if artemisinin resistance spreads to Africa.

A fallback therapy for malaria

After several years of progress, malaria control has stalled. An estimated 435,000 deaths occurred in 2017, with Africa accounting for 93% of deaths.

Malaria control is undermined by the development of drug resistance in malaria parasites. Although resistance to the mainstay of malaria treatment, artemisinin-based combination therapies, has not yet been widely seen in Africa, there are concerns that it could be introduced from South-East Asia and threaten the use of highly effective antimalarial therapies.

The challenge

The ASAAP project is evaluating the safety and efficacy of a novel triple therapy – combining artemether+lumefantrine (AL) and atovaquone–proguanil (AP, also known as Malarone). The AL combination is already widely used and is highly effective, but it is important that it is protected against the

development of resistance. Adding AP, another antimalarial with proven efficacy, will reduce the risk of resistance and have additional benefits. AP targets multiple stages of the malaria parasite life cycle, and may contribute to continuing protection after treatment and prevent the transmission of parasites to others.

The ASAAP project is organising primarily a pilot phase III study (in adults and adolescents) and a main phase III trial (in your children) in four African countries, comparing the AL–AP combination with AL on its own. The main trial will involve more than 1,500 children aged 6–59 months.

As well as cure rates at 42 days and safety, the trial will also look for any effects on re-infections, to assess post-treatment protection, and investigate the novel drug combination’s ability to block transmission of malaria parasites from blood samples to mosquitoes.

The project

The ASAAP project will contribute to preparedness in Africa for the emergence of artemisinin-resistant malaria parasites. It will determine whether AL–AP is a suitable alternative in such a situation, and whether it provides additional benefits by reducing human-to-mosquito transmission of malaria parasites.

Impact


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.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

After several years of progress, malaria control has stalled. An estimated 435,000 deaths occurred in 2017, with Africa accounting for 93% of deaths.

Malaria control is undermined by the development of drug resistance in malaria parasites. Although resistance to the mainstay of malaria treatment, artemisinin-based combination therapies, has not yet been widely seen in Africa, there are concerns that it could be introduced from South-East Asia and threaten the use of highly effective antimalarial therapies.

The ASAAP project is evaluating the safety and efficacy of a novel triple therapy – combining artemether+lumefantrine (AL) and atovaquone–proguanil (AP, also known as Malarone). The AL combination is already widely used and is highly effective, but it is important that it is protected against the

development of resistance. Adding AP, another antimalarial with proven efficacy, will reduce the risk of resistance and have additional benefits. AP targets multiple stages of the malaria parasite life cycle, and may contribute to continuing protection after treatment and prevent the transmission of parasites to others.

The ASAAP project is organising primarily a pilot phase III study (in adults and adolescents) and a main phase III trial (in your children) in four African countries, comparing the AL–AP combination with AL on its own. The main trial will involve more than 1,500 children aged 6–59 months.

As well as cure rates at 42 days and safety, the trial will also look for any effects on re-infections, to assess post-treatment protection, and investigate the novel drug combination’s ability to block transmission of malaria parasites from blood samples to mosquitoes.

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 ASAAP project will contribute to preparedness in Africa for the emergence of artemisinin-resistant malaria parasites. It will determine whether AL–AP is a suitable alternative in such a situation, and whether it provides additional benefits by reducing human-to-mosquito transmission of malaria parasites.

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

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M