CHAPAS-5: An Adaptive Platform Trial for Evaluation of Novel Treatment Regimens in ART-naive and Treatment-experienced Viraemic Children and Adolescents Living with HIV in Africa

Objective

The 2.5 million children and adolescents living with HIV (CALHIV), most residing in sub-Saharan Africa, have unacceptably high rates of late diagnosis, treatment failure and death, compared to their adult counterparts. CALHIV are a vulnerable group who have been left behind adults in testing new treatment options, different modes of ART delivery, novel diagnostics and adherence strategies. The CHAPAS-5 trial is a sustainable multi-country adaptive platform trial in Mozambique, Uganda and Zimbabwe, to assess novel treatment regimens in ART-naïve and treatment-experienced viraemic children aged 4 weeks to <20 years of age. CHAPAS-5 employs an innovative Personalised Randomised Controlled Trial (PRACTical) design, randomising participants between appropriate ART regimens based on their clinical status, ART history, genotypic resistance and drug availability by weight band. The trial's primary outcome is: alive with viral load <400 c/mL at 48 weeks. CHAPAS-5 will evaluate novel oral and first generation long-acting injectable (LAI) treatment regimens and, subsequently, through its adaptive design, second-generation promising long-acting therapeutics. Nested pharmacokinetics will evaluate dosing for children, as needed. Social science, health economics and capacity strengthening are fully integrated through the project. Workpackages will explore options for community-delivery of LAIs, and employment of diagnostics, including POC CD4, near-POC viral load and resistance tests. Community groups and young people will be involved in our dissemination and communication activities. We will exploit project outputs and facilitate technology transfer for treatments and diagnostics from innovators to African manufacturers. CHAPAS-5 aims to improve health and well-being of CALHIV, to inform clinical guidelines, and to strengthen health systems through capacity development. Our trial platform will provide a long-term resource for studies seeking to improve outcomes in CALHIV.