Vitamin D Status of HIV-Infected Women and Its Association with HIV Disease Progression, Anemia, and Mortality

Mehta, Saurabh; Giovannucci, Edward; Mugusi, Ferdinand; Spiegelman, Donna; Aboud, Said; Hertzmark, Ellen; Msamanga, Gernard; Hunter, David J.; Fawzi, Wafaie W.

doi:10.1371/journal.pone.0008770

Cited by 166 publications

(159 citation statements)

References 28 publications

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“…Vitamin D deficiency is associated with susceptibility to active TB in both the absence and the presence of HIV infection, but the association is stronger (24), suggesting a potential direct causal relationship between vitamin D deficiency and susceptibility to active TB. In HIV-infected people, vitamin D might also indirectly enhance antimycobacterial immunity by slowing progression of HIV disease (25,26), although studies investigating the effect of vitamin D metabolites on HIV replication in vitro report conflicting results (27)(28)(29)(30)(31). It is biologically plausible, therefore, that vitamin D deficiency impairs antimycobacterial responses in HIV-infected adults and that this phenomenon explains the association between vitamin D deficiency and susceptibility to active TB that we report here.…”

Section: Discussionmentioning

confidence: 67%

Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa

Martineau

Nhamoyebonde

Oni

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

183

181

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Vitamin D deficiency is associated with susceptibility to tuberculosis (TB) in HIV-uninfected people in Europe, but it is not known whether such an association exists among HIV-infected people in subtropical Africa. We conducted a cross-sectional study to determine whether vitamin D deficiency was associated with susceptibility to active TB in and HIV-infected (n = 174) black Africans in Cape Town, South Africa. We also investigated whether there was evidence of seasonal variation in vitamin D status and TB notifications in this setting over an 8-y period.nmol/L) was present in 232 (62.7%) of 370 participants and was associated with active TB in both HIV-uninfected (odds ratio = 5.2, 95% confidence interval: 2.8-9.7; P < 0.001) and HIV-infected (odds ratio = 5.6, 95% confidence interval: 2.7-11.6; P < 0.001) people. We have previously reported that vitamin D deficiency is associated with susceptibility to TB in London and that this association is modified by polymorphisms in the vitamin D receptor and vitamin D binding protein (8,9). We have also shown that in vivo vitamin D supplementation enhances immunity to mycobacteria both in healthy people (10) and in a genetically defined subgroup of patients with active TB (11). Reports of seasonal variation in the prevalence of vitamin D deficiency (12) and TB incidence (13) in the United Kingdom provide further evidence that low vitamin D status may compromise antimycobacterial immunity in this setting.The prevalence of profound vitamin D deficiency among TB patients in tropical Africa is much lower than in Europe [reported in 0.3-11.2% of patients with TB in tropical Africa (14-17) vs. 64-84% of patients with TB in ]. The prevalence of vitamin D deficiency in TB patients with and without HIV infection in subtropical Africa has not previously been reported. There is particularly good reason to investigate this question in Cape Town, South Africa, because TB incidence in Cape Town is higher than elsewhere in South Africa (21) and the ability of sunlight to synthesize vitamin D is compromised during the winter in Cape Town (latitude 33°south) but not in Johannesburg (latitude 26°south) (22). We therefore conducted an observational study to determine whether vitamin D deficiency is associated with susceptibility to active TB in HIVinfected and HIV-uninfected adults in Cape Town and to investigate whether there is evidence of seasonal variation in vitamin D status and TB notifications in this setting.

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Section: Discussionmentioning

confidence: 67%

Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa

Martineau

Nhamoyebonde

Oni

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

183

181

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“…Finally, vitamin D is an important immune modulator, can be tested in serum and considered as a confounder. 34 An example of a comprehensive sampling scheme Planning a sampling strategy for a clinical trial requires balancing of study objectives and endpoints, participant acceptability, available infrastructure and study budget.…”

Section: Confoundersmentioning

confidence: 99%

Methodological Issues in Sampling the Local Immune System of the Female Genital Tract in the Context of HIV Prevention Trials

Jespers

Francis

Wijgert

et al. 2010

American J Rep Immunol

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Citation  Jespers V, Francis SC, van de Wijgert J, Crucitti T. Methodological issues in sampling the local immune system of the female genital tract in the context of HIV prevention trials. Am J Reprod Immunol 2011; 65: 368–376 The spread of HIV continues unabated in the most vulnerable populations of the world. HIV prevention methods, such as a vaginal microbicide, a mucosal vaccine, pre‐exposure prophylaxis or a vaccine, are urgently needed in the fight against new infections. We must make a commitment to supporting innovative research and product design, so that one or more of these products provide a halt to the spread of HIV. Above all, these products should be proven to be safe and not negatively disturb the local immune system in a way that facilitates or enhances heterosexual transmission of HIV. HIV specific and non specific cellular and humoral local vaginal immunity must be assessed in clinical trials when testing prevention products for safety or efficacy. A proven, well‐documented and standardized sampling strategy will provide high quality data to be able to assess both safety and local immune responses. In this paper, we will discuss methods for vaginal immunology sampling in the context of clinical trials.

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“…This gives Correspondence: Dr. Mahdad Noursadeghi e-mail: m.noursadeghi@ucl.ac.uk way to the potential for vitamin D supplementation [1][2][3][4] or ex vivo conditioning of DCs with vitamin D for cell therapy strategies [5]. Vitamin D is synthesized from 7-dehydrocholesterol in the skin following exposure to ultraviolet B radiation and thermal isomerisation, or replenished by dietary intake.…”

mentioning

confidence: 99%

Regulation of CYP27B1 and CYP24A1 hydroxylases limits cell‐autonomous activation of vitamin D in dendritic cells

et al. 2014

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Keywords: CYP27B1 r CYP24A1 r DCs r Macrophages r Vitamin D Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionThe capacity of vitamin D metabolites to modulate macrophage and DC function has been subject to extensive research interest in light of the association of vitamin D deficiency with a broad spectrum of immunological and infectious diseases. This gives Correspondence: Dr. Mahdad Noursadeghi e-mail: m.noursadeghi@ucl.ac.uk way to the potential for vitamin D supplementation [1][2][3][4] or ex vivo conditioning of DCs with vitamin D for cell therapy strategies [5]. Vitamin D is synthesized from 7-dehydrocholesterol in the skin following exposure to ultraviolet B radiation and thermal isomerisation, or replenished by dietary intake. It is 25-hydroxylated in the liver to form 25-hydroxyvitamin D (25[OH]D), which is in * These authors contributed equally to this work. Results 25[OH]D is not functionally activated during monocyte differentiation to immature DCsWe first compared the activation of 25[OH]D during monocyte differentiation into macrophages and immature DCs. Conventional cell culture media in this model are vitamin D deficient (Fig. 1A) (Fig. 1B). This was also associated with upregulation of the prototypic vitamin D-inducible gene cathelicidin (CAMP) in macrophages (Fig. 1C) (Fig. 1C). Importantly, upregulation of DC-SIGN during monocyte differentiation to DCs was not affected by the presence of 1,25[OH] 2 D (Fig. 1D) DCs show time-dependent increase in activation of 25[OH]D independent of CYP27B1 expression levelsWe confirmed previous observations [16] that expression of the vitamin D-activating hydroxylase CYP27B1 is significantly lower in DCs compared with MDMs at both transcript and protein levels ( Fig. 2A and B). In contrast, vitamin D receptor (VDR) expression was higher in DCs than MDMs ( Fig. 2A). Taken together, these data further support the hypothesis that 25[OH]D has no effect on DCs in the experiments described above, because of a failure to generate 1,25[OH] 2 D rather than an inability to respond to 1,25[OH] 2 D. We also confirmed that 24-h stimulation of DCs with LPS significantly increases transcript and protein levels of CYP27B1 ( Fig. 2B and C (Fig. 2D). However, there was no concomitant upregulation of CAMP (Fig. 2C) . Monocytes are typically differentiated to DCs over 4-7 days, therefore we considered the possibility that time in culture may confound comparisons between different studies. Interestingly, we did find 25[OH]D-dependent upregulation of CAMP gene expression in DCs that increased with time after at least 6 days in culture (Fig. 2E). This was not associated with any significant time-dependent increase in CYP27B1 expression ( DCs express truncated CYP27B1 transcriptsWe found that LPS stimulation was able to upregulate DC expression of CYP27B1 transcript to levels higher than that in MDMs ( Figs. 2A and C). However, the expression of CYP27B1 protein remains much lower in DCs compared with ...

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Vitamin D Status of HIV-Infected Women and Its Association with HIV Disease Progression, Anemia, and Mortality

Cited by 166 publications

References 28 publications

Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa

Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa

Methodological Issues in Sampling the Local Immune System of the Female Genital Tract in the Context of HIV Prevention Trials

Regulation of CYP27B1 and CYP24A1 hydroxylases limits cell‐autonomous activation of vitamin D in dendritic cells

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