LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression leading to vitamin D consumption and hypovitaminosis D in HIV-infected individuals

AIM: Vitamin D deficiency is very common among HIV-infected subjects. Wecross-sectionally evaluated the prevalence and risk factors for hypovitaminosis Din 91 HIV-infected Italian patients.PATIENTS AND METHODS: We studied in a cohort of 91 HIV-infected Italian patients the metabolism of Vitamin D by evaluating the in vitro expression of CYP27B1,CYP24A1 and vitamin D receptor (VDR) by monocytes and macrophages stimulated withthe viral envelope protein gp120 or lipopolysaccharide (LPS).RESULTS: The prevalence of vitamin D deficiency (25OHD < 10 ng/ml) and vitamin D insufficiency (25OHD 10-30 ng/ml) was 31% and 57%, respectively. In univariateanalysis, female sex (p = 0.01), increasing age (p = 0.05), higher highlysensitive-C reactive protein (p = 0.025), higher parathyroid hormone (PTH) (p =0.043) and lower BMI (p = 0.04) were associated with vitamin D deficiency. Inmultivariate analysis, the association was still significant only for PTH (p =0.03) and female sex (p = 0.03). Monocyte stimulation with LPS (100 ng/ml) orgp120 (1 µg/ml) significantly upregulated CYP27B1 mRNA expression. Moreover,gp120 significantly increased VDR mRNA levels. On the contrary, neither LPS norgp120 modified CYP24A1 levels. Macrophage stimulation with LPS (100 ng/ml)significantly upregulated CYP27B1 and CYP24A1 mRNA expression. When monocyteswere cultured in the presence of 25OHD (40 ng/ml) and stimulated with LPS wedetected significantly lower levels of 25OHD in the supernatant.CONCLUSIONS: Vitamin D deficiency was very common in our cohort of HIV-infectedpatients. Chronic inflammation, including residual viral replication, maycontribute to hypovitaminosis D, by modulating vitamin D metabolism andcatabolism. Systematic screening may help identifying subjects requiringsupplementation.