Background: HIV-1-positive children and adolescents receiving antiretroviral therapy (ART) suffer high rates of treatment failure, predominantly caused by poor adherence to therapy and/or viral drug resistance. While high-income countries routinely use genotypic resistance testing (GRT), this diagnostic tool is not available in most low-income settings. For patients with a high viral load while on first-line ART, World Health Organisation guidelines recommend several months of adherence counselling followed by repeated viral load testing, with a sustained high viral load triggering a switch to an empirically selected second-line ART regimen.
Objective: We intend to assess whether early resistance testing could improve clinical outcomes for children and adolescents with viremia while on ART.
Methods: We will assess the clinical impact of GRT in an open-label randomised clinical trial enrolling 276 children and adolescents with an unsuppressed viral load (≥400 c/mL) while on a first-line ART regimen. Participants will be enrolled in Lesotho (four hospitals in three districts) and Tanzania (one hospital) and will be randomised to a control or intervention arm in a 1:1 allocation. The control arm will receive modified standard care, consisting of at least three sessions of adherence counselling followed by a follow-up viral load result which, if again unsuppressed (≥400 c/mL), will trigger a switch to an empirically selected second-line regimen. By contrast, the intervention arm will receive GRT (Sanger sequencing) and GRT-informed onward therapy. We will compare clinical outcomes (mortality, morbidity, viral suppression) at nine months.
Nested study: In a nested study, we will assess the cost and cost-effectiveness of the intervention.
Hypothesis: We expect to observe significantly better clinical outcomes in the intervention arm. Furthermore, we expect the implementation of GRT to be cost-effective.
Trial registration: clinicaltrials.gov/ct2/show/NCT04233242
Funding: Fondation Botnar (REG-19-008), Swiss National Science Foundation (PCEFP3_181355)