TOPLINE:

In adolescents with perinatally acquired HIV infection, weekly high-dose vitamin D3 plus daily low-dose calcium carbonate for 48 weeks did not significantly improve bone density or muscle function outcomes, but it significantly improved bone density of the lumbar spine in those who were vitamin D-insufficient at baseline.

METHODOLOGY:

• Researchers conducted a phase 3 randomized clinical trial to evaluate whether supplementation with high-dose vitamin D3 plus low-dose calcium carbonate improved bone density and muscle function in peripubertal adolescents with perinatally acquired HIV infection.
• They enrolled 842 participants (median age, 15 years; 53% girls) who had been on antiretroviral therapy for at least 6 months and randomly assigned them to receive chewable vitamin D3 (20,000 IU/wk) plus calcium carbonate (500 mg/d) or matching placebos for 48 weeks.
• The primary outcome was the Z score for total body less-head bone mineral density at 48 weeks, measured using DEXA.
• Secondary outcomes over the same period included Z scores for bone mineral apparent density of the lumbar spine, measured using DEXA; grip strength of the upper limb, measured using hand dynamometry; and muscle power of the lower limb, assessed using jump distance.
• Baseline vitamin D insufficiency was defined as a 25(OH)D concentration of less than 75 nmol/L.

TAKEAWAY:

• At 48 weeks, no significant between-group differences were observed in Z scores for total body less-head bone mineral density (adjusted mean difference, 0.04; 95% CI, -0.01 to 0.09) or in those for bone mineral apparent density of the lumbar spine (adjusted mean difference, 0.05; 95% CI, -0.01 to 0.12).
• Among participants with baseline vitamin D insufficiency, Z scores for bone mineral apparent density of the lumbar spine improved significantly with supplementation compared with placebo (adjusted mean difference, 0.09; P for interaction = .025).
• No significant differences were observed in the other secondary outcomes, including grip strength and muscle power. No drug-related severe adverse events were observed.

IN PRACTICE:

“Although the intervention appeared to be effective among those with vitamin D insufficiency, a pragmatic approach could be supplementation in all adolescents with HIV in settings with high prevalence of vitamin D insufficiency to circumvent the need for vitamin D testing,” the authors wrote.

SOURCE:

The study was led by Rashida A. Ferrand, PhD, London School of Hygiene & Tropical Medicine, London, England. It was published online on December 11, 2025, in The Lancet Child & Adolescent Health.

LIMITATIONS:

The trial assessed adherence through self-report and pill counts, which may have overestimated actual supplement use. The two study sites used different DEXA scanners. In the absence of local reference standards, Z scores were calculated using data from the UK.

DISCLOSURES:

The study was funded by the European & Developing Countries Clinical Trials Partnership program, supported by the European Union. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.