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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

The standard tool for detecting SARS-CoV-2 infections, PCR (polymerase chain reaction), requires transportation of samples to specialist facilities. This leads to delays in diagnosis. In addition, sub-Saharan Africa has relatively few facilities able to perform PCR. Developing a reliable and easy to use assay is therefore highly important.

Moreover, more information about epidemics can be obtained from whole genome sequencing. Sequence data can reveal how different SARS-CoV-2 infections are related, so that a more detailed picture of routes of transmission can be generated.

The RADIATES project is developing and evaluating a new approach for detecting SARS-CoV-2 genetic material. It is based on a technology known as ‘RT-LAMP’ (reverse transcriptional loop-mediated isothermal amplification), which forms the basis of promising diagnostics for a range of viral and bacterial infections. Unlike PCR, RT-LAMP does not require multiple cycles of heating and cooling, so is quicker to perform. It also generates easy-to-interpret results based on colour changes in analysed samples.

Having already developed a SARS-CoV-2 RT-LAMP test, the RADIATES Consortium is now optimising it for use in low-resource settings. Its performance will then be assessed in tests on 500 samples, with results being compared to those obtained with PCR.

Complementing this work, the RADIATES team will generate whole genome sequence data for a representative collection of samples from the Cape Town area. The sequences will be used to generate a family tree of genomes to shed light on how the virus has evolved and moved through the population over time.

These data will feed into a dynamic model of the spread of COVID-19 infection, which will be used to estimate key parameters such as reproduction number and how it has changed over time, as well as the number of people infected. The model will also be used to assess how public health interventions at various points affected the spread of infection, and to test the potential impact of other public health interventions, such as introduction of rapid point-of-care testing.

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.

An effective RT-LAMP test for SARS-CoV-2 would facilitate molecular diagnosis but without the need for centralised laboratory processing of samples. An RT-LAMP-based approach could be carried out in the community, and be quicker and cheaper than PCR, enabling isolation and contact tracing to begin immediately. In addition, the whole genome sequencing strand of work will provide detailed insight into the spread of COVID-19 in Cape Town, allowing comparisons to be made with other locations and providing a tool for evaluating the impact of public health interventions.

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