Project: VITamin D for AdoLescents with HIV to reduce musculoskeletal morbidity and ImmunopaThologY (VITALITY): an individually randomised, double-blinded placebo-controlled trial

Acronym	VITALITY (Reference Number: RIA2018CO-2512)
Duration	01/01/2020 - 31/12/2024
Project Topic	The global scale-up of antiretroviral therapy (ART) has dramatically increased survival of people with HIV. Hence, increasing numbers of children with HIV (CWH) who would previously have died in childhood are now reaching adolescence and adulthood. However, despite ART, CWH commonly experience chronic co-morbidities which result in disability and increased mortality risk; and ART alone is insufficient to maintain health and quality of life. HIV adversely impacts growth and bone health in children. Up to 50% of CWH experience growth failure, including stunting and pubertal delay. Puberty is a critical period for bone mass accrual, with peak bone mass (PBM) achieved at the end of puberty after linear growth ceases, and therefore disruption of growth impacts on skeletal development. HIV leads to immune activation which promotes bone resorption, leading to lower bone mass. Low PBM is a strong risk factor for osteoporosis and fragility fractures in adulthood, so interventions during childhood can have lifelong effects on health and well-being. Low dietary calcium and vitamin D deficiency, common in CWH even in countries with adequate sunshine, further compromise attainment of PBM and are risk factors for rickets and fractures; trials from high-income settings suggest that high-dose vitamin D supplementation promotes bone mineralisation and improves bone mass in CWH. Furthermore, vitamin D has immunomodulatory properties and supplementation may reduce HIV-mediated immunopathology. We will conduct a trial to evaluate the efficacy of high-dose vitamin D3 plus calcium carbonate in improving the musculoskeletal health of CWH in sub-Saharan Africa. The objectives are to investigate the effect of the intervention on i) bone mineral density (adjusting for body size); ii) bone turnover; iii) muscle mass and strength; and iv) immune regulation. The trial will be conducted in two countries with high HIV prevalence, Zimbabwe and Zambia, in partnership with institutions from UK and Germany. We will randomise 800 CWH aged 8 to 16 years taking ART to intervention or placebo for one year, with further follow-up for another year to investigate sustainability of the intervention effect. Capacity development for individuals and trial sites and networking activities will be central to project implementation. HIV and associated comorbidities is the leading cause of death in sub-Saharan Africa and an EDCTP2 category A priority. Our aim to prevent musculoskeletal morbidity among CWH therefore speaks strongly to the EDCTP2 strategic agenda, and to the research call to develop products for prevention of co-morbidities associated with proverty-related diseases.
Network	EDCTP2
Call	Advances in product development for effective prevention, treatment and management of co-infections and co-morbidities

Project partner

Number	Name	Role	Country
1	London School of Hygiene and Tropical Medicine	Coordinator	United Kingdom
2	Biomedical Research and Training Institute	Partner	Zimbawe
3	Forschungszentrum Borstel Leibniz-Zentrum für Medizin ud Biowissenschaften	Partner	Germany
4	The Chancellor, the Masters and the Scholars of the University of Oxford	Partner	United Kingdom
5	University of Bristol	Partner	United Kingdom
6	University Teaching Hospital	Partner	Zambia