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Current HIV/AIDS Reports
Published in: Current HIV/AIDS Reports 3/2014

01-09-2014 | Co-infections and Comorbidity (CM Wyatt and K Sigel, Section Editors)

Vitamin D Deficiency and Altered Bone Mineral Metabolism in HIV-infected Individuals

Authors: Allison Ross Eckard, Grace A. McComsey

Published in: Current HIV/AIDS Reports | Issue 3/2014

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Abstract

Although patients with HIV infection are living decades longer than before with the advent of combination antiretroviral therapy, they have an increased rate of co-morbidities associated with chronic HIV, such as osteoporosis, cardiovascular disease, and immune dysfunction. Many of these complications are known to be affected by vitamin D status in the general population. Thus, the high rate of vitamin D deficiency among HIV-infected patients is alarming. Many observational and cohort studies have demonstrated that vitamin D deficiency is associated with these HIV-related complications, but randomized, placebo-controlled trials are limited. This paper reviews recent data on vitamin D deficiency in HIV infection.
Literature
1.
Ross AC et al. Vitamin D is linked to carotid intima-media thickness and immune reconstitution in HIV-positive individuals. Antivir Ther. 2011;16(4):555–63.PubMedCentralPubMedCrossRef
2.
Eckard AR et al. Risk factors for vitamin D deficiency and relationship with cardiac biomarkers, inflammation and immune restoration in HIV-infected youth. Antivir Ther. 2012;17(6):1069–78.PubMedCrossRef
3.
Brown TT, McComsey GA. Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D. Antivir Ther. 2010;15(3):425–9.PubMedCrossRef
4.
Rutstein R et al. Vitamin D status in children and young adults with perinatally acquired HIV infection. Clin Nutr. 2011;30(5):624–8.PubMedCrossRef
5.
6.
Welz T et al. Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. AIDS. 2010;24(12):1923–8.PubMedCrossRef
7.•
Holick MF et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. This paper is a thorough and well-written summary of the current Endocrine Society guidelines for the evaluation, treatment, and prevention of vitamin D deficiency, with an emphasis on at-risk patients.PubMedCrossRef
8.
Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review.[see comment]. AIDS. 2006;20(17):2165–74.PubMedCrossRef
9.
Triant VA et al. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007;92(7):2506–12.PubMedCentralPubMedCrossRef
10.
Martinez E et al. Incidence and causes of death in HIV-infected persons receiving highly active antiretroviral therapy compared with estimates for the general population of similar age and from the same geographical area. HIV Med. 2007;8(4):251–8.PubMedCrossRef
11.
Wang TJ et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503–11.PubMedCrossRef
12.
Giovannucci E. Vitamin D status and cancer incidence and mortality. Adv Exp Med Biol. 2008;624:31–42.PubMedCrossRef
13.
14.
Ross AC, McComsey GA. The role of vitamin D deficiency in the pathogenesis of osteoporosis and in the modulation of the immune system in HIV-infected patients. Clin Rev Bone Miner Metab. 2012;10(4):277–87.CrossRef
15.
Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med (Berl). 2010;88(5):441–50.CrossRef
16.
Longenecker CT et al. Vitamin D supplementation and endothelial function in vitamin D deficient HIV-infected patients: a randomized placebo-controlled trial. Antivir Ther. 2012;17(4):613–21.PubMedCentralPubMedCrossRef
17.
Landriscina M et al. Reverse transcriptase inhibitors induce cell differentiation and enhance the immunogenic phenotype in human renal clear-cell carcinoma. Int J Cancer. 2008;122(12):2842–50.PubMedCrossRef
18.
Ellfolk M et al. Regulation of human vitamin D(3) 25-hydroxylases in dermal fibroblasts and prostate cancer LNCaP cells. Mol Pharmacol. 2009;75(6):1392–9.PubMedCrossRef
19.••
Overton E.T., et al. High-dose vitamin D and calcium attenuates bone loss with ART initiation: results from ACTG A5280, Abstract 133. Conference on Retroviruses and Opportunistic Infections, 2014. Boston, MA. This study is the first trial to evaluate vitamin D supplementation as a means to mitigate bone loss associated with ART initiation.
20.
Gupta SK et al. Effects of switching from efavirenz to raltegravir on endothelial function, bone mineral metabolism, inflammation, and renal function: a randomized, controlled trial. J Acquir Immune Defic Syndr. 2013;64(3):279–83.PubMedCrossRef
21.
Fox J et al. Improvement in vitamin D deficiency following antiretroviral regime change: Results from the MONET trial. AIDS Res Hum Retrovir. 2011;27(1):29–34.PubMedCrossRef
22.
Bischoff-Ferrari HA et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293(18):2257–64.PubMedCrossRef
23.
Dawson-Hughes B et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997;337(10):670–6.PubMedCrossRef
24.
Jackson RD et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669–83.PubMedCrossRef
25.
El-Hajj Fuleihan G et al. Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab. 2006;91(2):405–12.PubMedCrossRef
26.
Winzenberg TM et al. Vitamin D supplementation for improving bone mineral density in children. Cochrane Database Syst Rev. 2010;10, CD006944.PubMed
27.
McComsey GA et al. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS. 2007;21(18):2473–82.PubMedCrossRef
28.
Mondy K et al. Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection. J Acquir Immune Defic Syndr. 2005;38(4):426–31.PubMedCrossRef
29.•
Arpadi SM et al. Effect of supplementation with cholecalciferol and calcium on 2-y bone mass accrual in HIV-infected children and adolescents: a randomized clinical trial. Am J Clin Nutr. 2012;95(3):678–85. This study was one of the first to specifically evaluate the effects of vitamin D supplementation on bone in HIV-infected children and adolescents.PubMedCentralPubMedCrossRef
30.
Etminani-Esfahani M et al. Effects of vitamin D supplementation on the bone specific biomarkers in HIV infected individuals under treatment with efavirenz. BMC Res Notes. 2012;5:204.PubMedCentralPubMedCrossRef
31.
Gafni RI et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics. 2006;118(3):e711–8.PubMedCrossRef
32.
Kinai E, Hanabusa H. Renal tubular toxicity associated with tenofovir assessed using urine-beta 2 microglobulin, percentage of tubular reabsorption of phosphate and alkaline phosphatase levels. AIDS. 2005;19(17):2031–3.PubMedCrossRef
33.
Gallant JE et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. 2004;292(2):191–201.PubMedCrossRef
34.
Hazra R et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics. 2005;116(6):e846–54.PubMedCrossRef
35.
Jones S et al. Risk factors for decreased bone density and effects of HIV on bone in the elderly. Osteoporos Int. 2008;19(7):913–8.PubMedCrossRef
36.
McComsey GA et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203(12):1791–801.PubMedCentralPubMedCrossRef
37.
Calmy A et al. Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study. J Infect Dis. 2009;200(11):1746–54.PubMedCrossRef
38.
Mueller NJ et al. High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients. AIDS. 2010;24(8):1127–34.PubMedCrossRef
39.
Rosenvinge MM et al. Tenofovir-linked hyperparathyroidism is independently associated with the presence of vitamin D deficiency. J Acquir Immune Defic Syndr. 2010;54(5):496–9.PubMedCrossRef
40.
Childs KE et al. Short communication: Inadequate vitamin D exacerbates parathyroid hormone elevations in tenofovir users. AIDS Res Hum Retrovir. 2010;26(8):855–9.PubMedCentralPubMedCrossRef
41.
Havens PL et al. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial. Clin Infect Dis. 2012;54(7):1013–25.PubMedCentralPubMedCrossRef
42.
Havens PL et al. Serum 25-hydroxyvitamin D response to vitamin D3 supplementation 50,000 IU monthly in youth with HIV-1 infection. J Clin Endocrinol Metab. 2012;97(11):4004–13.PubMedCentralPubMedCrossRef
43.
Schleithoff SS et al. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2006;83(4):754–9.PubMed
44.
van Etten E et al. Regulation of vitamin D homeostasis: implications for the immune system. Nutr Rev. 2008;66(10 Suppl 2):S125–34.PubMedCrossRef
45.
46.
Wilkinson RJ et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet. 2000;355(9204):618–21.PubMedCrossRef
47.
48.
Cannell JJ et al. Diagnosis and treatment of vitamin D deficiency. Expert Opin Pharmacother. 2008;9(1):107–18.PubMedCrossRef
49.
50.
Williams B, Williams AJ, Anderson ST. Vitamin D deficiency and insufficiency in children with tuberculosis. Pediatr Infect Dis J. 2008;27(10):941–2.PubMedCrossRef
51.
Muhe L et al. Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children. Lancet. 1997;349(9068):1801–4.PubMedCrossRef
52.
Mehta S et al. Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality. PLoS One. 2010;5(1):e8770.PubMedCentralPubMedCrossRef
53.
Mehta S et al. Perinatal outcomes, including mother-to-child transmission of HIV, and child mortality and their association with maternal vitamin D status in Tanzania. J Infect Dis. 2009;200(7):1022–30.PubMedCentralPubMedCrossRef
54.••
Havers, F., et al. 25-Hydroxyvitamin D Insufficiency and Deficiency is Associated with HIV Disease Progression and Virological Failure Post-Antiretroviral Therapy Initiation in Diverse Multinational Settings. J Infect Dis, 2014. May 5. [Epub ahead of print]. In this case-cohort study, low 25(OH)D was an independent risk factor for increased risk of HIV progression and death and virologic failure after ART initiation.
55.•
Viard JP et al. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study. AIDS. 2011;25(10):1305–15. 25(OH)D deficiency was independently associated with a higher risk of mortality and AIDS events in a large observational cohort study of 1985 HIV-infected subjects.PubMedCrossRef
56.
57.
Shepherd, L., et al. Prognostic Value of Vitamin D Level for All-cause Mortality, and Association With Inflammatory Markers, in HIV-infected Persons. J Infect Dis, 2014.
58.•
Sudfeld CR et al. Vitamin D status and incidence of pulmonary tuberculosis, opportunistic infections, and wasting among HIV-infected Tanzanian adults initiating antiretroviral therapy. J Infect Dis. 2013;207(3):378–85. In this observational cohort study of ART-initiation in 1103 HIV-infected subjects in sub-Saharan Africa, vitamin D deficiency had a significantly greater association with incident pulmonary tuberculosis compared with vitamin D sufficiency.PubMedCentralPubMedCrossRef
59.
Nieto G et al. Association between AIDS disease progression rates and the Fok-I polymorphism of the VDR gene in a cohort of HIV-1 seropositive patients. J Steroid Biochem Mol Biol. 2004;89–90(1–5):199–207.PubMedCrossRef
60.
Roth DE et al. Association between vitamin D receptor gene polymorphisms and response to treatment of pulmonary tuberculosis. J Infect Dis. 2004;190(5):920–7.PubMedCrossRef
61.
de Luis DA et al. Relation among micronutrient intakes with CD4 count in HIV infected patients. Nutr Hosp. 2002;17(6):285–9.PubMed
62.
Teichmann J et al. Changes in calciotropic hormones and biochemical markers of bone metabolism in patients with human immunodeficiency virus infection. Metabolism. 2000;49(9):1134–9.PubMedCrossRef
63.
Van Den Bout-Van Den Beukel CJ et al. Vitamin D deficiency among HIV type 1-infected individuals in the Netherlands: effects of antiretroviral therapy. AIDS Res Hum Retrovir. 2008;24(11):1375–82.PubMedCrossRef
64.
Arpadi SM et al. Effect of bimonthly supplementation with oral cholecalciferol on serum 25-hydroxyvitamin D concentrations in HIV-infected children and adolescents. Pediatrics. 2009;123(1):e121–6.PubMedCentralPubMedCrossRef
65.
66.
Liu PT et al. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol. 2007;179(4):2060–3.PubMedCrossRef
67.
Yuk JM et al. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. 2009;6(3):231–43.PubMedCrossRef
68.
Bergman P et al. The antimicrobial peptide LL-37 inhibits HIV-1 replication. Curr HIV Res. 2007;5(4):410–5.PubMedCrossRef
69.
Campbell GR, Spector SA. Hormonally active vitamin D3 (1alpha,25-dihydroxycholecalciferol) triggers autophagy in human macrophages that inhibits HIV-1 infection. J Biol Chem. 2011;286(21):18890–902.PubMedCentralPubMedCrossRef
70.
Frohm Nilsson M et al. The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6. Infect Immun. 1999;67(5):2561–6.PubMedCentralPubMed
71.
Levinson P et al. Levels of innate immune factors in genital fluids: association of alpha defensins and LL-37 with genital infections and increased HIV acquisition. AIDS. 2009;23(3):309–17.PubMedCrossRef
72.
Mahon BD et al. The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells. J Cell Biochem. 2003;89(5):922–32.PubMedCrossRef
73.
Bhalla AK et al. 1,25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol. 1984;133(4):1748–54.PubMed
74.
Lemire JM et al. Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr. 1995;125(6 Suppl):1704S–8.PubMed
75.
Mattner F et al. Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D(3). Eur J Immunol. 2000;30(2):498–508.PubMedCrossRef
76.
Pittas AG et al. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92(6):2017–29.PubMedCentralPubMedCrossRef
77.
Boucher BJ et al. Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. Diabetologia. 1995;38(10):1239–45.PubMedCrossRef
78.
Reis JP et al. Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics. 2009;124(3):e371–9.PubMedCrossRef
79.
Forouhi NG et al. Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Diabetes. 2008;57(10):2619–25.PubMedCentralPubMedCrossRef
80.
81.
82.
Schleithoff SS et al. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial.[see comment]. Am J Clin Nutr. 2006;83(4):754–9.PubMed
83.
London GM et al. Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency.[see comment]. J Am Soc Nephrol. 2007;18(2):613–20.PubMedCrossRef
84.
Rahman A et al. Heart extracellular matrix gene expression profile in the vitamin D receptor knockout mice. J Steroid Biochem Mol Biol. 2007;103(3–5):416–9.PubMedCrossRef
85.
Tishkoff DX et al. Functional vitamin D receptor (VDR) in the t-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility. Endocrinology. 2008;149(2):558–64.PubMedCentralPubMedCrossRef
86.
Simpson RU, Hershey SH, Nibbelink KA. Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J Steroid Biochem Mol Biol. 2007;103(3–5):521–4.PubMedCentralPubMedCrossRef
87.
88.
Choi AI et al. Association of vitamin D insufficiency with carotid intima-media thickness in HIV-infected persons. Clin Infect Dis. 2011;52(7):941–4.PubMedCentralPubMedCrossRef
89.
Lai H et al. Vitamin D deficiency is associated with development of subclinical coronary artery disease in HIV-infected African American cocaine users with low Framingham-defined cardiovascular risk. Vasc Health Risk Manag. 2013;9:729–37.PubMedCentralPubMedCrossRef
Metadata
Title
Vitamin D Deficiency and Altered Bone Mineral Metabolism in HIV-infected Individuals
Authors
Allison Ross Eckard
Grace A. McComsey
Publication date
01-09-2014
Publisher
Springer US
Published in
Current HIV/AIDS Reports / Issue 3/2014
Print ISSN: 1548-3568
Electronic ISSN: 1548-3576
DOI
https://doi.org/10.1007/s11904-014-0218-8

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