Vitamin D dysregulation can occur in people living with HIV, disrupting calcium homeostasis and bone turnover. We aimed to investigate the potential mechanisms by which vitamin D regulates bone turnover in adolescents living with perinatally-acquired HIV (ALWH) in southern Africa. A pre-planned secondary analysis was performed of baseline data from the VITALITY trial [PACTR20200989766029] which enrolled ALWH (11-19 years) taking antiretroviral therapy for ≥6 months, and recorded socio-demographic, clinical and dietary data. After over-night fasting, vitamin D metabolites [25(OH)D, 1,25(OH)2D, 24,25(OH)2D], intact parathyroid hormone (PTH) and bone turnover markers (BTMs) [CTX and P1NP] were measured. Tandem Mass Spectrometry measured vitamin D metabolites, whilst intact PTH and BTMs were analysed by electrochemiluminescence immunoassay. Stratified by 25(OH)D [<75 vs ≥75 nmol/L], associations between standardized concentrations (β = standard deviations) of vitamin D metabolites, intact PTH and BTMs were assessed using structural equations modelling (SEM) adjusted for age, sex and country (Zimbabwe/Zambia). Among the 842 ALWH enrolled, the median dietary calcium intake was 100 mg [IQR:55-145]. The SEM showed PTH was positively associated [β 0.21, 95%CI: 0.1,0.32] with 1,25(OH)2D, only when 25(OH)D was <75 nmol/L vs ≥75 nmol/L [β 0.23, 95%CI: -0.13,0.59], with evidence of an interaction [β -0.11, 95%CI: -0.20,-0.02]. A positive relationship between 25(OH)D and 24,25(OH)2D was seen irrespective of 25(OH)D concentration. 24,25(OH)2D was inversely related to BTMs, particularly when 25(OH)D was <75 nmol/L [CTX: β -0.15, 95%CI: -0.24,-0.06, and P1NP: β -0.14, 95%CI: -0.22,-0.06]. There was interaction between dietary calcium and 25(OH)D on PTH [β -0.15, 95% CI: -0.22,-0.07] suggesting an interaction between low 25(OH)D and low dietary calcium which increases PTH. In conclusion, associations between 25(OH)D, PTH, 1,25(OH)2D and BTMs in ALWH appear dependent upon 25(OH)D concentrations <75 nmol/L and calcium intake. A novel, potentially causal pathway between 25(OH)D, 24,25(OH)2D and BTMs was seen. Findings enhance understanding of vitamin D metabolism in people living with HIV.
Keywords: Africa; Hiv; parathyroid hormone; vitamin d.
Vitamin D plays an important role in regulating calcium and supporting bone health particularly during puberty when the body needs extra nutrients to support rapid growth. However, many people living with HIV often have low vitamin D, which may be because HIV disrupts how the body processes vitamin D, or because of certain HIV treatments like tenofovir-disoproxil-fumarate, or, in Africa people have low calcium diets. We researched adolescents, age 11 to 19 years, living with HIV in Zimbabwe and Zambia, with low calcium diets. We investigated how important hormones control vitamin D and how this relates to bone activity, and growth. The findings suggest adolescents living with HIV need higher levels of vitamin D than has traditionally been thought. Our research also discovered a new link between a vitamin D breakdown product [called 24,25(OH)2D], and suggests this might play its own role influencing bone activity and development. These findings provide new understanding of vitamin D and its actions in people living with HIV in Africa. In addition the study findings might inform vitamin D supplementation programs in adolescents living with HIV to target achieving higher vitamin D levels to see improvements in bone health.
© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.