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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

As countries in sub-Saharan Africa scale up antiretroviral treatment (ART) programs, more in utero exposure to antiretroviral (ARV) drugs will occur among children born to HIV-infected women. ART use in pregnancy has been associated with preterm birth (birth < 37 weeks gestational age). This further increases the already elevated risk for preterm birth among HIV-exposed infants and preterm birth is associated with increased neonatal mortality. However, among HIV-exposed infants born preterm, neither differential risk of HIV-acquisition nor toxicity of antiretroviral prophylaxis in the first month of life has been well studied.

Dr Ajibola conducts an evaluation of the relationship between preterm birth and a) mother-to-child HIV transmission (MTCT), and b) antiretroviral prophylaxis toxicity. The specific aims of the study are, first, to describe the prevalence and timing (in utero versus peripartum) of MTCT in HIV-exposed infants delivered preterm vs those delivered at term in the setting of ART. Secondly, Dr Ajibola aims to assess the haematologic safety of ARV prophylaxis among HIV-exposed infants born preterm in the first month of life, evaluating for anaemia and/or neutropenia. He uses data collected from infants that participated in a randomised controlled trial looking at the effect of cotrimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu study, R01HD061265).

He proposes to analyse the number of infants with positive HIV-DNA PCR at birth or within 72 hours postdelivery (for in utero transmission) and at 4-6 weeks post-delivery (for peripartum transmission) and compare these rates for preterm birth vs at term infants. To conduct the analysis of adverse haematologic comparisons between HIV-exposed preterm and at term infants receiving ARV prophylaxis, the occurrence of anaemia and neutropenia will be compared, using a grade 3 or greater value of haemoglobin or absolute neutrophil count per the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events version 2 (November 2012), using data from infants enrolled in the Mpepu Study.

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 findings of the study will quantify the extent to which preterm birth confers an increased risk of mother-to-child transmission of HIV. The study has the potential to inform public policy with regards to testing and prophylaxis strategies for preterm HIV-exposed infants. As 1 in 5 HIV-exposed infants are born preterm in resource-constrained settings, these findings may contribute to improved survival and a reduction in overall neonatal and infant mortality. Furthermore, the study will provide data on the efficacy and haematological safety of prophylactic ARV regimens in preterm infants.

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