CHAPAS-5

The challenge

An estimated 1.4 million children and 1 million adolescents are living with HIV, around 90% of them in sub-Saharan Africa. Every year, 140,000 adolescents become infected with HIV, two-thirds of them girls. 

Children and adolescents experience worse outcomes than adults living with HIV: although they make up 3% of people living with HIV, children account for 13% of HIV-related deaths. Adolescents are significantly less likely to achieve good suppression of viral replication and also experience higher mortality rates than adults.

Initial clinical trials of new treatments typically exclude children and adolescents, and new formulations may need to be developed for adolescents, leading to long delays in access. For a commonly used treatment, dolutegravir, there was a seven-year gap between initial licensing and its first use in young children.

This is an increasingly important issue, as the treatments currently used have significant drawbacks. Several new treatment options are becoming available, including dolutegravir/lamivudine combinations, triple antiretroviral therapy (ART) incorporating tenofovir alafenamide (TAF), and long-acting injectables (such as cabotegravir and lenacapavir) that do not require daily pill-taking.

The project

The CHAPAS consortium has been working for more than 20 years to enhance young people’s access to novel HIV treatments. The CHAPAS-5 project aims to go a step beyond trials that compare new and existing regimens by establishing an innovative adaptive clinical trial platform. Encompassing sites in Mozambique, Uganda, and Zimbabwe, the platform will be able to test multiple treatment options simultaneously across a range of patient groups.

The project will recruit two main groups of patients: those about to start their first antiretroviral treatment and those who are already receiving antiretrovirals but have developed resistant infections, and, therefore, need to be switched from first-line to second-line back-up treatment. 

For each group, patients will be randomised to either the currently recommended treatment or to possible alternatives already used in adults (provided at least two options exist). As these treatments have already been shown to be effective in adults, the key aim is to rank each option by efficacy and safety.

This approach can also be used to assess efficacy and safety in different subgroups of patients, such as those in particular weight bands, generating more nuanced evidence to guide the choice of treatment. The project will initially focus on the above combinations, but the platform will also enable the evaluation of other emerging treatment options in young people.

The project also includes pharmacokinetic studies to determine whether dosing is appropriate for different age groups. In addition, it will explore whether a range of new technologies, such as point-of-care testing for viral load and/or immune cell counts, hepatitis B virus testing, and local-level genome sequencing to identify resistance mutations, can also improve patient care and outcomes. 

Embedded within the project is a strong social science strand that will focus on adherence among adolescents and treatment preferences. This is particularly important, as uncontrolled viral replication in adolescents is more likely to reflect lack of adherence than drug resistance. The project will also explore the feasibility of a new approach to care, community-based dosing, which will provide young people with easier access to antiretrovirals through community health workers.

Impact

The CHAPAS-5 project will make a major contribution to the treatment of HIV infections in children and adolescents. It will:

• Provide a highly efficient and cost-effective way to generate data on multiple new first-line and second-line antiretroviral treatments.
• Provide decision-makers with data on multiple possible treatment options and indicate which would be most suitable for particular groups of patients.
• Establish a platform for testing new treatments in young people as they become available.
• Evaluate other innovations that could have a significant impact on retention in care and adherence.
• Explore options to ensure the availability and accessibility of preferred antiretroviral drugs, for example, through local manufacturing.

In sum, the CHAPAS-5 project will accelerate young people’s and adolescents’ access to newly developed HIV treatments and ensure that care is better tailored to their needs, helping to reduce the excessive burden of disease in these vulnerable groups.