A third of children hospitalised with severe acute malnutrition in sub-Saharan Africa also have HIV, and they die at three times the rate of children with malnutrition alone. Current treatments fail to fix this, because the problem is not just biological—it is also social. Poverty, weak caregivers, and repeated infections trap these children in a cycle of relapse and hospital readmission after discharge. This programme will first map the biological and social pathways that keep children from recovering. Using existing samples and qualitative fieldwork, the team will identify which infections, nutrient deficiencies, and caregiver vulnerabilities matter most. They will then design three intervention packages—one to prevent infections, one to improve nutrient absorption, and one to provide psychosocial support for caregiver-child pairs. In an adaptive trial across Kenya, Zimbabwe, and Zambia, 732 children will be randomised to receive one, all, or none of these packages for 12 weeks. The primary outcome is death or hospitalisation within 24 weeks. If successful, the research could produce a cost-effective, scalable package of care that cuts mortality, reduces re-admissions, and supports healthy growth and neurodevelopment in a high-burden region.
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Background One-third of children hospitalised with severe acute malnutrition (SAM) in sub-Saharan Africa have HIV infection (HIV-SAM). Children with HIV-SAM have 3-fold higher mortality, slower nutritional recovery and a higher risk of relapse compared to children with SAM alone, despite current interventions. Mortality following hospital discharge is predominantly driven by infections, compounded by poor nutritional convalescence. Moreover, children are discharged to homes characterised by poverty and multiple caregiver vulnerabilities. Addressing this complex multimorbidity requires a deeper understanding of the underlying biological and social pathways to inform new intervention approaches. Aims and Objectives Our aim is to define causal pathways underlying multimorbidity in HIV-SAM, and to develop and test multimodal interventions addressing the biological and social factors preventing convalescence. Our objectives are: Characterise the multimorbidity of HIV-SAM to identify tractable pathways for intervention. Develop multimodal packages of interventions for children with HIV-SAM. Test the effects of single and combined biomedical and psychosocial interventions on morbidity and mortality, and determine the cost-effectiveness and mechanism of action of the intervention packages. Methods Our interdisciplinary programme unites two networks of researchers in southern and east Africa and will be conducted in three stages. In Stage 1, we will leverage existing samples and data from each network to characterise HIV-SAM multimorbidity. We will use targeted and exploratory omics-based techniques to undertake molecular characterisation of HIV-SAM to identify tractable biological pathways for intervention. We will define the social and environmental determinants of HIV-SAM through in-depth qualitative research to understand the contexts in which child convalescence occurs. In Stage 2, we will develop and optimise intervention packages aimed at (i) preventing infections; (ii) improving nutrient bioavailability; and (iii) enhancing psychosocial support for caregiver-child pairs. In Stage 3, interventions will be tested in an adaptive clinical trial in Kenya, Zimbabwe and Zambia. We will recruit 732 children with HIV-SAM at the time of hospital discharge and randomise them to: (i) a double-sized control arm, (ii) anti-infection arm, (iii) nutrition arm, (iv) psychosocial arm, and (v) a combination of all intervention packages for 12 weeks. The primary composite outcome will be morality or hospitalisation by 24 weeks, with secondary outcomes of morbidity, growth, neurodevelopment, HIV viral load, CD4 count, and adverse events. Mechanistic sub-studies will define mechanisms of action for each intervention. Process evaluation and health economics evaluations will inform feasibility and cost-effectiveness of interventions. Timelines for delivery Stage 1 and Stage 2 will last 18 months. In Stage 3, trial enrolment will take 2 years, with 6 months of follow-up. Anticipated Impact and Dissemination Malnutrition and HIV impair child survival and human capital in high-burden countries. An effective package of care for children with HIV-SAM would reduce mortality, decrease hospital re-admissions and promote healthy growth and neurodevelopment. We will disseminate findings to participants through community advisory boards and caregiver meetings; to researchers through academic papers, policy briefs and media channels; and to policymakers through our partnerships with Ministries of Health and UNICEF, which will help to sustainably scale-up effective approaches.
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