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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

Despite the great success of programmes to eliminate mother-to-child transmission of HIV – an estimated 1.3 million cases were averted between 2010 and 2015 – large numbers of infants continue to be infected with HIV in Africa. In 2016, around 160,000 children became infected with HIV.

In addition, death rates from HIV are highest in infants aged 0–4 years. Infants who acquire HIV via maternal transmission are thus a highly vulnerable group.

Co-Director of the Uganda Laboratory Core C, part of the Joint Clinical Research Centre, Dr Immaculate Nankya has contributed to numerous landmark trials of HIV/AIDS treatment and clinical studies on HIV/AIDS. She has a particular interest in the detection of mutations that confer resistance to antiretroviral drugs.

In her EDCTP Senior Fellowship, Dr Nankya aims to ensure that HIV-infected infants receive the best possible care. Currently, infants are started on antiretroviral treatment regimens without any assessment of the presence of drug resistance mutations. Dr Nankya is using next-generation DNA sequencing technology to determine the prevalence of drug resistance mutations, including extremely rare ones, using dried blood spot samples. Infants will be monitored for three years to determine whether the mutations detected have any impact on response to therapy.

Importantly, next-generation DNA sequencing may detect rare HIV variants not identified by standard DNA sequencing technologies. Under drug selection pressure, these rare variants may expand and ultimately trigger treatment failure.

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 Nankya’s Senior Fellowship project will provide key data on how drug resistance mutations affect treatment responses in a very vulnerable population. They will have the potential to feed directly into national and international guidelines of recommended programmes of care for HIV-infected infants.

The Uganda Laboratory Core C has also developed into a sophisticated centre for molecular virology and immunology. It provides an ideal site for the training of young scientists from Uganda and elsewhere in Africa on the latest laboratory techniques, including next-generation DNA sequencing. Dr Nankya’s fellowship will include training of two master’s students.

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