The effect of antiretrovirals on vitamin D.

There has been growing interest in vitamin D status and metabolism in patients with human immunodeficiency virus (HIV). Osteoporosis and fractures, as well as many of the extraskeletal conditions associated with vitamin D deficiency, including diabetes, dyslipidemias, and cardiovascular disease [1], are increasingly recognized in HIV-infected individuals. The relationships of these complications to vitamin D status among HIV-infected patients, as well as the effects of antiretroviral therapy (ART) on vitamin D metabolism, are important areas of research. In addition, as a result of the known effects of vitamin D on innate and adaptive immunity [2–4], there is growing interest in determining whether vitamin D deficiency increases the risk of inadequate immune reconstitution, opportunistic infections, and AIDS-related mortality. Recent data from a cohort of pregnant HIV-infected women in Tanzania who were given multivitamin supplementation (not including vitamin D) revealed that vitamin D insufficiency/deficiency at baseline was associated with increased risks of HIV disease progression, anemia, and all-cause mortality, as well as mother-to-child transmission of HIV [5, 6]. Vitamin D, in the form of cholecalciferol, or vitamin D3, is synthesized in the epidermis when UV-B exposure is adequate. Additional vitamin D can be obtained from diet and supplements, in the form of ergocalciferol (D2) from plant sources or cholecalciferol from animal sources. Vitamin D from cutaneous manufacture or dietary intake is converted by one of several high-capacity cytochrome P450s to 25-hydroxy vitamin D (25OHD). This form of vitamin D is the most stable and abundant metabolite and is therefore the best indicator of an individual’s vitamin D status [7]. Conversion of 25OHD to the active form of vitamin D, 1,25(OH)2D, is catalyzed by the mitochondrial enzyme CYP27B1hydroxylase. This enzyme is principally located in the proximal tubular epithelial cells of the kidney, where its activity is stimulated by parathyroid hormone and inhibited by fibroblast growth factor-23. In addition, 1,25(OH)2D induces the expression of the enzyme 25-hydroxyvitamin D-24-hydroxylase (CYP24), which catabolizes both 25OHD and 1,25(OH)2D into inactive calcitroic acid [1]. Many extrarenal tissues, including monocytes/macrophages, also contain the enzyme CYP27B1, as well as the vitamin D receptor. The vitamin D receptor is a member of the superfamily of nuclear hormone receptors. It functions as a heterodimer with the retinoid X receptor for regulation of vitamin D target genes [8]. In these extrarenal tissues, 1,25(OH)2D acts as a local cytokine. In monocytes, interaction of 1,25(OH)2D with the vitamin D receptor modulates the innate immune response to invading microbes [7]. This process has been shown to be dependent on the availability of adequate serum concentrations of 25OHD and increases in response to vitamin D supplementation [9] In this issue of the journal, Dao et al [10] use baseline data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN), involving a prospective observational cohort of HIV-positive adults from the United States, to estimate the prevalence of vitamin D insufficiency/deficiency, defined as serum 25OHD levels of ,30 ng/mL, in comparison with data from the National Health and Nutrition Examination Surveys (NHANES) database. Multivariate models involving HIV-infected participants were used to determine risk factors for vitamin D insufficiency/deficiency. The age-, race-, and sex-adjusted prevalence of vitamin D insufficiency/ deficiency was high among HIV-infected individuals (70%) but lower than that among US adults (79%) from the NHANES database. Among HIV-infected individuals, factors associated with vitamin D insufficiency/deficiency in multivariate analysis were non-Caucasian race, higher body mass index, hypertension, lack of exercise, decreased UV exposure, Received 29 October 2010; accepted 18 November 2010. Correspondence: Michael Yin, MD, Columbia University Medical Center, New York, New York. Clinical Infectious Diseases 2011;52(3):406–408 2011 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2011/523-0001$37.00 DOI: 10.1093/cid/ciq169