Vitamin D supplementation is associated with reduced immune activation levels in HIV-1-infected patients on suppressive antiretroviral therapy.

BACKGROUND: A majority of HIV-1-infected patients present a severe deficit in vitamin D, which predicts short-term mortality. Vitamin D is a naturally synthesized hormone, with important immunomodulatory functions. In the general population, its deficit has been associated with increased markers of inflammation. Vitamin D deficit may therefore play a role in the establishment of elevated systemic immune activation, which persists despite suppressive antiretroviral therapy (ART) in HIV-infected patients, and is predictive of disease progression; and vitamin D supplementation may be beneficial in this context. METHODS: We performed both a cross-sectional study (vitamin D deficit versus normal level) and a longitudinal study (upon vitamin D supplementation for 6 to 12 months) of HIV-1-infected patients receiving suppressive ART. The primary outcome measure was the percentage of activated memory CD8(+) T cells in blood, which is a robust marker associated with disease progression. Secondary outcomes included general T-lymphocyte and B-lymphocyte phenotype. RESULTS: Although vitamin D deficiency had no influence on T-cell and B-cell subset distribution, we found an association between vitamin D and immune activation levels in HIV-1-infected patients. Vitamin D supplementation in vitamin D-deficient patients resulted in reduced immune activation levels. CONCLUSION: The present data support the rationale of vitamin D supplementation in the routine clinical management of HIV-1-infected patients, in order to decrease immune activation levels and possibly improve long-term survival.

Vitamin D3 supplementation scheme in HIV-infected patients based upon pharmacokinetic modelling of 25-hydroxycholecalciferol.

AIMS: Vitamin D deficiency is prevalent in HIV-infected patients and has been associated with osteopenia and HIV disease progression. Our aims were to investigate the pharmacokinetics of 25-hydroxycholecalciferol [25(OH)D], the effect of antiretroviral treatment (ARV) and others factors that may influence the pharmacokinetics, and to determine a vitamin D3 dosing scheme to reach the 30 ng ml(-1) threshold (defined as 25(OH)D sufficiency). METHODS: This monocentric retrospective study included 422 HIV-infected patients aged 16 to 85 years. A total of 723 25(OH)D concentrations were available for pharmacokinetic evaluation and a population pharmacokinetic model was developed with MONOLIX 3.2. RESULTS: Median 25(OH)D at baseline was 16 ng ml(-1) (interquartile range 11-23 ng ml(-1)) for the total population, 17% of patient had concentrations below 10 ng ml(-1), 68% between 10 and 30 ng ml(-1) and 15% above 30 ng ml(-1). 25(OH)D pharmacokinetics were best described by a one compartment model with an additional endogenous production. The effects of season and skin phototype were significant on production rate. The endogenous production was 20% lower in non-white skin phototype patients and was decreased by 16% during autumn, winter and spring. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs (ARV). To obtain concentrations between 30 and 80 ng ml(-1), the dosing recommendation was 100,000 IU every month. CONCLUSIONS: Season and skin phototype had an influence on the endogenous production of 25(OH)D. However no effect of ARV was found. A dosing scheme to reach sufficient 25(OH)D concentrations is proposed.