{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:39:19Z","timestamp":1775151559533,"version":"3.50.1"},"reference-count":47,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,11,1]]},"abstract":"<jats:p>The serum level of 1,25-dihydroxyvitamin D3[ 1,25-(OH)2D], the biologically most potent metabolite of vitamin D, is tightly regulated within narrow limits in human healthy adults. 1,25-(OH)2D deficiency is rare and is associated with disturbances in calcium and bone metabolism. We have previously reported a marked decrease in serum levels of 1,25-(OH)2D in human immunodeficiency virus (HIV)-infected patients. The present study was designed to further examine the causes and consequences of severe 1,25-(OH)2D deficiency in these patients. The design was a prospective cohort study. Fifty-four HIV-infected patients clinically classified according to the revised criteria from Centers for Disease Control and Prevention and healthy controls were studied. Parameters related to vitamin D and calcium metabolism as well as immunological and nutritional status were determined. Twenty-nine of the patients (54%) had serum levels of 1,25-(OH)2D below the lower reference limit, and 18 of these had undetectable levels. In contrast, HIV-infected patients had normal serum levels of 25-hydroxyvitamin D and vitamin D-binding protein. HIV-infected patients as a group had modestly depressed serum calcium and PTH levels. There were, however, no correlations between these parameters and serum levels of 1,25-(OH)2D. There were no differences in serum calcium or PTH levels or nutritional status when patients with severe 1,25-(OH)2D deficiency were compared to other patients, but patients with undetectable 1,25-(OH)2D had significantly elevated serum phosphate levels. Furthermore, patients with undetectable 1,25-(OH)2D levels were characterized by advanced clinical HIV infection, low CD4+ lymphocyte counts, and high serum levels of tumor necrosis factor-\u03b1 (TNF\u03b1).<\/jats:p><jats:p>We conclude that inadequate 1\u03b1-hydroxylation of 25-hydroxyvitamin D seems to be the most likely cause of 1,25-(OH)2D deficiency in HIV-infected patients, possibly induced by an inhibitory effect of TNF\u03b1. The low 1,25-(OH)2D and high TNF\u03b1 levels observed may impair the immune response in HIV-infected patients both independently and in combination and may represent an important feature of the pathogenesis of HIV-related immunodeficiency. Markedly depressed 1,25-(OH)2D serum levels are also present in certain other disorders characterized by immunological hyperactivity. Thus, the findings in the present study may not only represent a previously unrecognized immune-mediated mechanism for induction of 1,25-(OH)2D deficiency in human disease, but may also reflect the importance of adequate serum levels of 1,25-(OH)2D for satisfactory performance of the immune system in man.<\/jats:p>","DOI":"10.1210\/jcem.83.11.5270","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:02:29Z","timestamp":1389200549000},"page":"3832-3838","source":"Crossref","is-referenced-by-count":137,"title":["Severe Deficiency of 1,25-Dihydroxyvitamin D3 in Human Immunodeficiency Virus Infection: Association with Immunological Hyperactivity and Only Minor Changes in Calcium Homeostasis"],"prefix":"10.1210","volume":"83","author":[{"given":"Charlotte J.","family":"Haug","sequence":"first","affiliation":[{"name":"Section of Clinical Immunology and Infectious Diseases, Medical Department A, and Research Institute for Internal Medicine, University of 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and Infectious Diseases, Medical Department A, and Research Institute for Internal Medicine, University of Oslo (C.J.H., P.A., F.M., S.S.F.), Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stig S.","family":"Fr\u00f8land","sequence":"additional","affiliation":[{"name":"Section of Clinical Immunology and Infectious Diseases, Medical Department A, and Research Institute for Internal Medicine, University of Oslo (C.J.H., P.A., F.M., S.S.F.), Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071618323613300_R1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1365-2796.1993.tb00730.x","article-title":"Effects of age, sex, season and diet on serum ionized calcium, parathyroid hormone and vitamin D in a random population.","volume":"234","author":"Rudnicki","year":"1993","journal-title":"J Intern 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