Genotype-Informed Versus Empiric Management Of VirEmia (GIVE MOVE): study protocol of an open-label randomised clinical trial in children and adolescents living with HIV in Lesotho and Tanzania

Abstract

Background: Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART).

Methods: GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at 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, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up.

Discussion: This randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART.

Trial registration: This trial is registered with ClinicalTrials.gov ( NCT04233242 ; registered 18.01.2020). More information: www.givemove.org .

Keywords: Adolescents; Antiretroviral therapy; Children; Drug resistance; Genotypic resistance testing; HIV; Randomised clinical trial; Sub-Saharan Africa; Treatment failure.

Conflict of interest statement

TK reports advisory board membership fees from ViiV and Gilead for work outside of this study. All other authors declare that they have no competing interests.

Figures

Fig. 1

Flow chart of GIVE MOVE treatment algorithm and study visits. Detailed procedures at each study visit are listed in Fig. 2. GRT: genotypic resistance testing; VL: viral load

Fig. 2

SPIRIT diagram of study procedures. Footnotes: 1 Conducted 24 weeks (range: 20–28 weeks) after the visit in which the follow-up viral load result (control arm) or the GRT result (intervention arm) is first available; may coincide with another study visit. 2 May be delayed upon evidence of poor adherence, defined as a pill count of <90% and/or a self-reported period of no drug intake of ≥2 days in the last 4 weeks. 3 In intervention arm: informed by GRT result. 4 Clinical information at ART initiation; previous ART regimens; exposure to prevention to mother-to-child transmission strategies. 5 Height, weight, middle upper arm circumference (if aged <5 years), nutritional status. 6 WHO stage; co-morbidities; symptoms and side-effects; new hospitalisation. 7 Female participants aged ≥12 years. GRT: genotypic resistance testing; VL: viral load