“
crucial in

widening African

children’s access

to antiretrovirals

”

Bringing antiretroviral drugs to children

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

The challenge

An effective HIV vaccine is likely to be key to controlling the HIV epidemic. Unfortunately, HIV is very difficult to target with vaccines and past trials have had limited success. However, the RV144 trial in Thailand did find that a DNA vaccine ‘prime’ followed by a protein vaccine ‘boost’ appeared to offer modest levels of protection.

Nevertheless, more innovative approaches may be needed. One possibility is pre-exposure prophylaxis (PrEP), in which high-risk populations receive antiretroviral dugs to prevent HIV infection.

The PrEPVacc trial is combining these two approaches to HIV prevention in a large-scale phase II trial. It will assess the impact of two experimental HIV vaccine regimens, already tested and shown to be safe in people, when used alongside antiretroviral-based PrEP. The vaccine regimens both combine DNA-based and protein-based elements, as used in the RV144 trial.

The trial will be carried out in high-risk populations in four sub-Saharan African countries. It also includes an innovative design feature: PrEPVacc will be an ‘adaptive’ trial, so that combinations can be halted mid-trial if they are turning out to be ineffective – the first time this approach has been adopted in an HIV vaccine trial.

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.

PrEPVacc will generate the first evidence of the ability of vaccine plus PrEP combinations to prevent HIV infections – information that would have major public health importance. It will also provide key data on the ability of the experimental vaccines to stimulate protective immune responses, and the likely success of DNA plus protein prime–boost vaccine strategies. Data on the nature of the immune responses triggered by the vaccines may also reveal which are key to prevention of HIV infection.

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