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test the safety and efficacy of this new formulation in young children

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Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Malaria in pregnancy (MIP) may result in serious clinical consequences for mother and child. In moderate- to high-transmission areas of sub-Saharan Africa, the World Health Organization (WHO) recommends the use of long-lasting insecticidal nets (LLINs) together with Intermittent Preventive Treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) and/or treatment of confirmed cases.

However, there are concerns that IPTp-SP efficacy is becoming less as a consequence of the ever-increasing parasite resistance to SP. Continued use of SP for IPTp would result in further reduction of IPTp-SP efficacy and compromise the prevention of MIP-associated adverse outcomes. As SP needs to remain the recommended antimalarial drug for IPTp, the challenge is to devise strategies to prevent and treat which avoid furthering SP-resistance of the parasite.

Reducing SP interaction with the already mutated parasite would prevent further selection of mutated parasites, reduce resistance to SP and improve its efficacy. This may be achieved by introducing at the first antenatal care (ANC) visit, a malaria Rapid Diagnostic Testing (mRDT). Mothers testing positive will then be treated with a fully effective antimalarial drug before being administered SP; mothers testing negative will receive SP as per current recommendations.

Therefore, Dr Kubuya proposed to compare the current IPTp-SP treatment with IPTp-SP in combination with an mRDT and treatment at the first ANC visit (IPTp-SP+) in terms of efficacy at clearing peripheral maternal parasitaemia and prevention of adverse outcomes associated with MIP. Volunteer mothers not infected with HIV and meeting the inclusion criteria will be recruited for this clinical trial. Relevant socio-demographic and clinical information is collected and blood samples are taken for haemoglobin and malaria molecular testing at enrolment, days 14, 28, 42 and 63, and at delivery. In addition, cord blood and a placental biopsy will be collected, and babies’ haemoglobin will be measured to determine malaria parasitology and histopathology.

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.

Data from this study may directly help MIP leaders to review current practice for the prevention of malaria in pregnancy. Positive outcomes will expand the available medical interventions for this special population and contribute to averting resistance to SP.

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