The CHAPAS 4 study aims to identify a suitable second-line therapy for children with HIV who are not responding to first-line drugs.

Back-up treatment for children with HIV

WHO now recommends that all children with HIV infections should be given antiretroviral drugs. A projected 2.3 million children are likely to be taking antiretroviral drugs by 2020.

Although antiretroviral therapy is highly effective in children, not all children respond as well as others. In addition, as more children take antiretroviral drugs for longer periods, drug-resistant infections will inevitably emerge. Documented levels of treatment failure vary widely in Africa, but can be as high as 50%. Treatment failure requires a shift to second-line antiretroviral therapy. However, current formulations for second-line treatments have significant drawbacks, being based on whole pills, mini-pill pellets, or unpleasant liquids, and limited data are available on their use in children.

The challenge

For more than a decade, the CHAPAS Consortium has organised clinical trials to improve the treatment options available for children with HIV in sub-Saharan Africa. Data from EDCTP-funded CHAPAS 1 and CHAPAS 3 projects supported licensing applications for children-specific formulations and provided evidence in support of WHO recommendations on updated treatment options, opening the door to more extensive use of antiretroviral therapy in African children.

The CHAPAS 4 study is designed to identify an optimal second-line treatment for children with HIV infections. The study, being carried out in three sub-Saharan countries, will use an innovative trial design to compare a range of possible options. These include formulations incorporating dolutegravir, a relatively new drug with significant advantages over existing treatments; atazanavir/ritonavir (ATV/r), which is now available in a single pill suitable for children; and tenofovir–alafenamide (TAF), a tenofovir pro-drug that may be particularly suitable for use in children, co-formulated with emtricitabine. These agents will be tested in different combination regimens against the current standard of care for children.

The project will also explore interactions between antiretroviral drugs and anti-TB medications, and their impact on the effectiveness of treatment and toxicity. It will also examine the cost implications of the new treatments. 

The project

CHAPAS 4 will generate key data on multiple second-line options for children in whom first-line antiretroviral therapy is failing – a vulnerable group that is destined to grow as use of antiretroviral drugs increases. In particular, the innovative trial design will enable comparisons to be made between multiple treatment options in a single clinical trial. The study will also provide important evidence on treatment options for children who are infected with TB as well as HIV.

Impact


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.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

WHO now recommends that all children with HIV infections should be given antiretroviral drugs. A projected 2.3 million children are likely to be taking antiretroviral drugs by 2020.

Although antiretroviral therapy is highly effective in children, not all children respond as well as others. In addition, as more children take antiretroviral drugs for longer periods, drug-resistant infections will inevitably emerge. Documented levels of treatment failure vary widely in Africa, but can be as high as 50%. Treatment failure requires a shift to second-line antiretroviral therapy. However, current formulations for second-line treatments have significant drawbacks, being based on whole pills, mini-pill pellets, or unpleasant liquids, and limited data are available on their use in children.

For more than a decade, the CHAPAS Consortium has organised clinical trials to improve the treatment options available for children with HIV in sub-Saharan Africa. Data from EDCTP-funded CHAPAS 1 and CHAPAS 3 projects supported licensing applications for children-specific formulations and provided evidence in support of WHO recommendations on updated treatment options, opening the door to more extensive use of antiretroviral therapy in African children.

The CHAPAS 4 study is designed to identify an optimal second-line treatment for children with HIV infections. The study, being carried out in three sub-Saharan countries, will use an innovative trial design to compare a range of possible options. These include formulations incorporating dolutegravir, a relatively new drug with significant advantages over existing treatments; atazanavir/ritonavir (ATV/r), which is now available in a single pill suitable for children; and tenofovir–alafenamide (TAF), a tenofovir pro-drug that may be particularly suitable for use in children, co-formulated with emtricitabine. These agents will be tested in different combination regimens against the current standard of care for children.

The project will also explore interactions between antiretroviral drugs and anti-TB medications, and their impact on the effectiveness of treatment and toxicity. It will also examine the cost implications of the new treatments. 

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.

CHAPAS 4 will generate key data on multiple second-line options for children in whom first-line antiretroviral therapy is failing – a vulnerable group that is destined to grow as use of antiretroviral drugs increases. In particular, the innovative trial design will enable comparisons to be made between multiple treatment options in a single clinical trial. The study will also provide important evidence on treatment options for children who are infected with TB as well as HIV.

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

Projects: CAPRISA 018 study

Project lead: Professor Salim Abdool Karim, Centre for the AIDS Programme of Research in South Africa, South Africa

Countries involvedFrance, The Netherlands, South Africa

Target population(s): Women

Year funded: 2017

EDCTP funding: €9.8 M

Total project funding: €11.4M plus donation of study drugs

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

Contact us

For more information, please contact us or leave a message using this form.
Please enter your name
Please enter a correct e-mail address
Please enter a comment
Thank you! Your message has been sent.
Something went wrong while submitting the form. Try again.

Share this publication

Forward this page by e-mail or share it directly on social media.

Search

Enter a search term to search the EDCTP publications.
Minimal length to search is 3 characters

This publication uses cookies

We use functional and analytical cookies to improve our website. In addition, third parties place tracking cookies to display personalised advertisements on social media. By clicking accept you consent to the placement of these cookies.