Genotype-Informed Versus Empiric Management of VirEmia (GIVE MOVE) in HIV-Infected Children and Adolescents on Antiretroviral Therapy: An Open-Label Randomised Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 286
- 试验地点
- 10
- 主要终点
- Composite primary endpoint
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In care in a study site
- •Age ≥6 months and <19 years
- •Latest HIV viral load result ≥400 c/mL
- •On an unchanged ART regimen for ≥6 months
- •Phlebotomy for latest viral load test <4 months before screening
- •Consent given
排除标准
- •Indication for treatment switch according to WHO guidelines at screening
- •1st enhanced adherence counselling (EAC) session initiated >2 weeks prior to screening
- •Intention to transfer out of the study site (and not into a different study site) within 3 months after randomisation
- •Already enrolled in another study if judged as non-compatible by the (Local) Principal Investigator
- •Pregnant or breastfeeding at screening (no exclusion based on pregnancy or breastfeeding after enrolment)
- •Acute illness requiring hospitalisation at screening (no exclusion based on hospitalisation after enrolment)
- •Received a resistance test in the last 12 months
结局指标
主要结局
Composite primary endpoint
时间窗: At 9 months follow-up visit (window: 32-44 weeks)
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, judged by the endpoint committee blinded to the study arm) during the follow-up period (36 weeks), iii) new clinical World Health Organization (WHO) stage IV event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis; judged by the endpoint committee blinded to the study arm) during the follow-up period (36 weeks), and iv) no documentation of a suppressed viral load (\<50 c/mL) at 9 months follow-up (window: 32-44 weeks). The primary endpoint will be assessed as an event ratio of participants reaching one or more of the composite endpoints.
次要结局
- Proportion lost to follow-up(At 9 months follow-up visit (window: 32-44 weeks))
- Proportion with death due to any cause(Within 36 weeks after baseline)
- Composite endpoint(6 months (window: 20-28 weeks) after the decision on onward treatment)
- Proportion with HIV- or ART-related hospital admission of ≥24 hours duration(Within 36 weeks after baseline)
- Proportion with new clinical WHO stage IV event(s) (with some exclusions)(Within 36 weeks after baseline)
- Proportion without documentation of a suppressed viral load(At 9 months follow-up visit (window: 32-44 weeks))
- Proportion with observed virologic failure(At 9 months follow-up visit (window: 32-44 weeks))