Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial

Abstract

Background Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. Methods/design We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11–19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMCLBMZ-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. Discussion This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. Trial registration Pan African Clinical Trials Registry PACTR20200989766029. Registered on 3 September 2020

The Efficacy of Calcium Carbonate-Vitamin D3 in Pregnant Women for the Prevention of Hypertensive Disorders in Pregnancy

“…In recent years, with the improvement of people' understanding of the function of calcium in human physiology, it is believed that the occurrence of gestational hypertension may be associated with calcium [ 7 ]. Clinical research has found that the calcium requirement of the maternal body increases significantly at about 20 weeks of gestation [ 8 ], and at about 30 weeks, the calcium requirement of the maternal body can be about 6 times higher than that at 20 weeks, so the maternal body is prone to calcium deficiency in the second trimester [ 9 ].…”

Perinatal HIV infection is associated with deficits in muscle function in children and adolescents in Zimbabwe

“…Interestingly, in one study of vitamin D supplementation trial among 81 CWH in the USA, an improvement in jump power was observed, albeit in an exploratory post hoc analysis [42]. Whether vitamin D supplementation can improve muscle function in African CWH is currently subject to clinical trial [43].…”

“…Interestingly, in one study of vitamin D supplementation trial among 81 CWH in the USA, an improvement in jump power was observed, albeit in an exploratory post hoc analysis [42]. Whether vitamin D supplementation can improve muscle function in African CWH is currently subject to clinical trial [43]. In male individuals, lower muscle density (indicating greater intramuscular fat) partially mediated the negative effect of HIV infection on jump power.…”