Publications

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

EDCTP portfolio: Malaria

The PYRAPREG study is exploring whether pregnant women can benefit from a newly developed safe and effective antimalarial drug.

Expanding the options for malaria control in pregnancy

Malaria in pregnancy can be harmful to both mother and child, causing maternal anaemia and low birth weight. In 2015, it was the third most common cause of death of women of reproductive age in Africa. Malaria in pregnancy is responsible for around 400,000 cases of maternal anaemia and 15% of maternal deaths globally.

Several artemisinin-based combination therapies are recommended for treatment of malaria in the second and third trimesters of pregnancy, but they vary in their efficacy, safety and tolerability. Pyronaridine–artesunate (PA) is a relatively new artemisinin-based combination therapy that could be a suitable alternative but it has yet to be evaluated in pregnancy.

The challenge

The PYRAPREG study is carrying out a large-scale evaluation of PA use in pregnant women in five African countries. The safety and efficacy of PA will be compared with those of two other commonly used artemisinin-based combination therapies, dihydroartemisinin–piperaquine and artemether–lumefantrine.

The main aim of the trial is to determine if PA is as good as the comparator treatments, with acceptable safety and tolerability. The pharmacokinetics of PA are also being monitored, and any influence of antiretroviral medications examined in a subset of women with HIV infections.

The project

The PYRAPREG study will determine whether a relatively new drug with some attractive features – for example, it only needs to be taken once a day, does not need to be eaten with fatty food, and has a relatively long half-life – is suitable for use in pregnant women.

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

Malaria in pregnancy can be harmful to both mother and child, causing maternal anaemia and low birth weight. In 2015, it was the third most common cause of death of women of reproductive age in Africa. Malaria in pregnancy is responsible for around 400,000 cases of maternal anaemia and 15% of maternal deaths globally.

Several artemisinin-based combination therapies are recommended for treatment of malaria in the second and third trimesters of pregnancy, but they vary in their efficacy, safety and tolerability. Pyronaridine–artesunate (PA) is a relatively new artemisinin-based combination therapy that could be a suitable alternative but it has yet to be evaluated in pregnancy.

The PYRAPREG study is carrying out a large-scale evaluation of PA use in pregnant women in five African countries. The safety and efficacy of PA will be compared with those of two other commonly used artemisinin-based combination therapies, dihydroartemisinin–piperaquine and artemether–lumefantrine.

The main aim of the trial is to determine if PA is as good as the comparator treatments, with acceptable safety and tolerability. The pharmacokinetics of PA are also being monitored, and any influence of antiretroviral medications examined in a subset of women with HIV infections.

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 PYRAPREG study will determine whether a relatively new drug with some attractive features – for example, it only needs to be taken once a day, does not need to be eaten with fatty food, and has a relatively long half-life – is suitable for use in pregnant women.

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