Abstract

Background: Children and adolescents living with HIV experience high rates of treatment failure. In most countries with a high prevalence of HIV, access to drug resistance testing to guide the selection of antiretroviral drugs is extremely limited. The GIVE MOVE trial assesses the clinical impact and cost-effectivenessof providing genotypic resistance testing (GRT) to children and adolescents with HIV experiencing viremia despite antiretroviral therapy (ART).

Methods: GIVE MOVE (NCT04233242) is an open-label, parallel-group randomised clinical trial enrolling 276 children and adolescents living with HIV with a viral load (VL) ≥400 c/mL while on ART. Recruitment takes place in 10 sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test informing onward treatment, and an empirical selection of the onward drug regimen) and an intervention arm (GRT using Sanger sequencing and expert committee recommendation to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the events i) death due to any cause during the follow-up period (36 weeks), ii) HIV- or ART-related hospital admission of ≥24 hours duration (possibly, probably or definitely related to HIV or ART) during the follow-up period (36 weeks), iii) new clinical WHO stage IV event (with some exclusions) during the follow-up period (36 weeks), and iv) no documentation of a VL <50 c/mL at 9 months follow-up (window: 32-44 weeks).

Discussion: GRT is widely used in high-income countries but access is limited in many other settings. As the cost of GRT decreases and rates of pre-treatment drug resistance rise, the clinical impact and feasibility of broader implementation must be explored. Given their heightened vulnerability and increased rate of treatment failure, children and adolescents are expected to benefit disproportionately from this diagnostic tool.