Genotype-Informed Versus Empiric Management of VirEmia
Condition: HIV-1-infection
MeSH terms: Viremia
Study type: Interventional

Summary: 
      HIV infection can be effectively controlled with antiretroviral therapy (ART). However,
      children and adolescents living with HIV and receiving ART suffer high rates of treatment
      failure, predominantly caused by suboptimal adherence to therapy and/or viral drug
      resistance. While high-income countries routinely use genotypic resistance testing (GRT) to
      determine which drug combinations are likely to be effective, this diagnostic tool is
      relatively costly and labour-intensive and is not routinely available in most
      resource-limited settings.

      GIVE MOVE is a multi-country (Lesotho, Tanzania) randomised clinical trial assessing if rapid
      GRT after detecting an unsuppressed viral load improves the clinical management and thus
      health outcomes for children and adolescents living with HIV. Children and adolescents with
      an unsuppressed viral load despite ART are enrolled and randomly allocated to a control or an
      intervention arm (50% of participants in each arm). The control arm receives care according
      to the current standard of care, consisting of three sessions of enhanced adherence
      counselling at monthly intervals, followed by a second viral load test. Onward treatment is
      informed by the outcome of this viral load test alongside empirical guidelines and clinical
      judgement. The intervention arm receives GRT and GRT-informed onward therapy. Participants in
      the intervention arm also receive three sessions of enhanced adherence counselling, which is
      informed by GRT results (i.e., if no drug resistance is detected, there is a high chance of
      suboptimal adherence to ART and this can be directly addressed).

      This trial will assess if the rapid provision of GRT improves participants' health outcomes
      at 9 months after enrolment. A nested study will assess the cost and cost-effectiveness of
      GRT. Thus, this trial will provide evidence on whether the provision of GRT for children and
      adolescents with HIV should be prioritised in resource-limited settings.
    

Detailed description: 
      Background and rationale:

      Children and adolescents living with HIV and receiving antiretroviral therapy (ART) suffer
      high rates of treatment failure, predominantly caused by suboptimal adherence to therapy
      and/or viral drug resistance. While high-income countries routinely use genotypic resistance
      testing (GRT) to select an optimal ART regimen, this diagnostic tool is not routinely
      available in many resource-limited settings.

      Objective:

      The GIVE MOVE trial assesses if rapid GRT after detection of an unsuppressed viral load in
      children and adolescents on ART improves health outcomes when compared to the current
      standard of care. Furthermore, a nested study will assess the cost-effectiveness of this
      intervention. Combined, these results will provide evidence on whether GRT should be
      prioritised for children and adolescents with HIV.

      Study design:

      GIVE MOVE is a multi-centre (several centres in 2 countries, Lesotho and Tanzania),
      parallel-group (1:1 allocation), open-label randomised clinical trial. Children and
      adolescents living with HIV with a viral load ≥400 c/mL are enrolled.

      The control group is managed as per the current standard of care that follows the World
      Health Organization guidelines, i.e. three sessions of enhanced adherence counselling at
      monthly intervals, followed by a second viral load test and viral load-informed onward
      treatment.

      In the intervention arm, participants receive GRT, a GRT-informed treatment recommendation by
      a GRT Expert Committee, and GRT-informed onward therapy, selecting the best locally available
      drugs according to the drug resistance profile.

      The GIVE MOVE trial will compare clinical outcomes (mortality, morbidity, viral suppression;
      see the Primary Outcome section for the composite primary endpoint) at nine months. Assuming
      that 20% vs 35% reach the primary endpoint in the intervention vs control arm, and at a
      significance level of 5%, 276 participants (138 per arm) are required to reach 80% power.

      In addition to clinical outcomes, the trial intends to assess the cost and cost-effectiveness
      of the intervention. The GIVE MOVE trial aims at informing future clinical guidelines on the
      management of paediatric HIV.
    

Intervention name(s): Clinical management informed by HIV-1 genotypic resistance testing
Intervention type(s): Other
Intervention description(s): The study intervention will consist of the following components:
Genotypic resistance testing (GRT);
Review of GRT results by an expert committee providing a treatment recommendation;
GRT-based decision on further therapy (switch or maintain current ART regimen; choice of regimen); and
GRT-informed adherence support.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Multi-centre, open-label, parallel-group (1:1 allocation), superiority randomised clinical trial
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: HIV-1; acquired immunodeficiency syndrome; drug resistance; treatment failure; child; adolescent; Lesotho; Tanzania