25-hydroxyvitamin-d-2 and HIV-Infections

Toll-like receptors (TLR) are important in recognizing microbial pathogens and triggering host innate immune responses, including autophagy, and in the mediation of immune activation during human immunodeficiency virus type-1 (HIV) infection. We report here that TLR8 activation in human macrophages induces the expression of the human cathelicidin microbial peptide (CAMP), the vitamin D receptor (VDR) and cytochrome P450, family 27, subfamily B, polypeptide 1 (CYP27B1), which 1α-hydroxylates the inactive form of vitamin D, 25-hydroxycholecalciferol, into its biologically active metabolite. Moreover, we demonstrate using RNA interference, chemical inhibitors and vitamin D deficient media that TLR8 agonists inhibit HIV through a vitamin D and CAMP dependent autophagic mechanism. These data support an important role for vitamin D in the control of HIV infection, and provide a biological explanation for the benefits of vitamin D. These findings also provide new insights into potential novel targets to prevent and treat HIV infection.

Topics: 25-Hydroxyvitamin D 2; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Antimicrobial Cationic Peptides; Autophagy; Cathelicidins; Female; HIV Infections; HIV-1; Humans; Ligands; Male; Receptors, Calcitriol; Toll-Like Receptor 8; Vitamins

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

Topics: 25-Hydroxyvitamin D 2; Adult; Dietary Supplements; Disease Susceptibility; Female; Genitalia, Female; HIV Infections; HIV-1; Humans; Immunologic Factors; Middle Aged; Mucous Membrane; Nutritional Status; Pilot Projects; Vitamin D; Vitamin D Deficiency; Young Adult

To determine the prevalence of vitamin D deficiency (VDD) in adult medical, non-tuberculous (non-TB) patients. To investigate associations with VDD. To compare the results with a similar study in TB patients at the same hospital.. Cross-sectional sample.. Central hospital in Malawi.. Adult non-TB patients (n = 157), inpatients and outpatients.. The primary outcome was the prevalence of VDD. Potentially causal associations sought included nutritional status, in/outpatient status, HIV status, anti-retroviral therapy (ART) and, by comparison with a previous study, a diagnosis of tuberculosis (TB).. Hypovitaminosis D (≤75 nmol/L) occurred in 47.8% (75/157) of patients, 16.6% (26/157) of whom had VDD (≤50 nmol/L). None had severe VDD (≤25 nmol/L). VDD was found in 22.8% (23/101) of in-patients and 5.4% (3/56) of out-patients. In univariable analysis in-patient status, ART use and low dietary vitamin D were significant predictors of VDD. VDD was less prevalent than in previously studied TB patients in the same hospital (68/161 = 42%). In multivariate analysis of the combined data set from both studies, having TB (OR 3.61, 95%CI 2.02-6.43) and being an in-patient (OR 2.70, 95%CI 1.46-5.01) were significant independent predictors of VDD.. About half of adult medical patients without TB have suboptimal vitamin D status, which is more common in in-patients. VDD is much more common in TB patients than non-TB patients, even when other variables are controlled for, suggesting that vitamin D deficiency is associated with TB.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Aged; Cross-Sectional Studies; Female; HIV Infections; Hospitals, General; Humans; Malawi; Male; Middle Aged; Prevalence; Risk Factors; Tuberculosis; Vitamin D Deficiency; Young Adult

Vitamin D deficiency is very common among HIV-infected subjects. We cross-sectionally evaluated the prevalence and risk factors for hypovitaminosis D in 91 HIV-infected Italian patients.. 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 with the viral envelope protein gp120 or lipopolysaccharide (LPS).. 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 univariate analysis, female sex (p = 0.01), increasing age (p = 0.05), higher highly sensitive-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. In multivariate 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) or gp120 (1 µg/ml) significantly upregulated CYP27B1 mRNA expression. Moreover, gp120 significantly increased VDR mRNA levels. On the contrary, neither LPS nor gp120 modified CYP24A1 levels. Macrophage stimulation with LPS (100 ng/ml) significantly upregulated CYP27B1 and CYP24A1 mRNA expression. When monocytes were cultured in the presence of 25OHD (40 ng/ml) and stimulated with LPS we detected significantly lower levels of 25OHD in the supernatant.. Vitamin D deficiency was very common in our cohort of HIV-infected patients. Chronic inflammation, including residual viral replication, may contribute to hypovitaminosis D, by modulating vitamin D metabolism and catabolism. Systematic screening may help identifying subjects requiring supplementation.

Topics: 25-Hydroxyvitamin D 2; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adult; Cells, Cultured; DNA Primers; Female; HIV Envelope Protein gp120; HIV Infections; Humans; Interleukin-6; Lipopolysaccharides; Macrophages; Male; Middle Aged; Monocytes; Multivariate Analysis; Real-Time Polymerase Chain Reaction; Steroid Hydroxylases; Vitamin D; Vitamin D Deficiency; Vitamin D3 24-Hydroxylase

Decreased bone mineral density (BMD) was reported in HIV infected patients. Mechanisms leading to this decrease are poorly understood.. To assess factors relating to BMD in young HIV infected Israeli women of Ethiopian and Caucasian origin.. 75 young HIV infected women aged 34.5 ± 8.5 followed up at the Institute of Allergy, Clinical Immunology & AIDS filled a questionnaire about sun exposure, daily calcium intake and dress habits. Data about HIV status and treatment regimens were collected from the patients' charts. Serum hydroxyvitamin D [25(OH)D] levels, bone turnover markers and bone densitometry were evaluated.. 28 (65%) of Ethiopians and 2 (6.25%) of Caucasians had 25(OH)D serum levels <10 ng/ml (vitamin D deficiency), p = 0.001. 21 (67.7%) Ethiopians and 16 (39%) Caucasians avoided sun exposure, p = 0.019. Mean daily calcium intake was 491 ± 268.6 mg and 279 ± 252.6 mg, respectively, p = 0.001. Z scores < -1 found at Lumbar spine in 26 (89.7%), at Femoral neck in 20 (69%) at Total hip in 17 (58.6%) of vitamin D deficient patients compared to 20 (48.8%), 17 (41.5%), 9 (22%), in patients with 25(OH)D > 10 ng/ml, p < 0.01, <0.03, <0.001, respectively. Significantly more Ethiopian than Caucasian women covered their face (32.3% and 9.5%, p = 0.003) and hands (58.1% and 30.9%, p = 0.03). There was no difference in bone turnover markers levels.. Poorer vitamin D status was observed in Ethiopian women might be one of the important factors related to lower BMD in this group.

Topics: 25-Hydroxyvitamin D 2; Biomarkers; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Calcifediol; Calcium, Dietary; Clothing; Diet; Ethiopia; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Israel; Middle Aged; Nutritional Status; Osteoporosis; Sunlight; Vitamin D Deficiency; White People