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

”

Bringing antiretroviral drugs to children

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

The challenge

Emerging and reemerging infections are a major threat to global health today. Their occurrence is unpredictable and they often cause serious morbidity, mortality as well as economic losses. The world needs to be better prepared to handle an outbreak anytime and this requires surveillance to detect outbreaks. The challenge is to develop the tools to assess and control the threat.

Dr Masika and his team will conduct a cross-sectional study on patients with acute febrile illness in three health facilities in the Kibera informal settlement, Nairobi city, Kenya. Sociodemographic and clinical data, as well as blood and urine samples, will be collected from 384 patients with fever for up to 5 days and no signs of localising.

Samples will be analysed using ELISA for antibodies against flaviviruses, alphaviruses and bunyaviruses. Positive samples will be further analysed using plaque reduction neutralisation assays to differentiate the specific viruses. Group-specific PCR will be done to detect any viruses from the three groups (flaviviruses, alphaviruses and bunyaviruses); Sanger sequencing will be performed on PCR-positive samples to determine the specific virus. In addition, the samples will be analysed using next-generation sequencing to detect any other viruses in the samples. Bioinformatics and phylogenetic analysis will be used to assess the genomic diversity of any arboviruses sequenced. Sociodemographic, clinical and laboratory data will be statistically analysed (SPSS).

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.

This study will determine the proportion of acute febrile illness that is due to arboviruses. Any novel or emerging viruses will also be identified and characterised. This information will help in surveillance efforts as well as the selection and development of appropriate diagnostic assays and vaccine targets for common arboviral infections in the study area and beyond.

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