Vitamins have essential roles in metabolic processes. Vieth r 2007 vitamin d toxicity, policy, and science. Efavirenz is associated with severe vitamin d deficiency and. Although the only 50,000iu preparation available by prescription from pharmacies in the united states is vitamin d 2, vitamin d 3 is more. Metabolic complications of efavirenz gary maartens division of clinical pharmacology university of cape town iyunivesithi yasekapa universiteit van kaapstad. Efv induces the metabolism of vitamin d, resulting in lower concentrations efv independently associated with lower bone mineral density in a crosssectional study in cape town plos one 1012. Metabolic complications of hiv infection journal of. Background initiation of efavirenz based combination antiretroviral therapy cart is associated with vitamin d deficiency, but the risk factors for cartinduced severe vitamin d deficiency svdd and the impact of antituberculosis tb cotreatment is not explored well. Aug 18, 2015 hiv infection and antiretroviral therapy art may create unique risk factors for vitamin d insufficiency, including alterations of vitamin d metabolism by art.
Efavirenz treatment and falsepositive results in benzodiazepine screening tests. Substitution of vitamin d 3 and calcium did not result in normal serological bone metabolism markers. After changing the antiretroviral regimen from efavirenzboosted to ritonavirboosted saquinavir, the laboratory parameters began to normalize. Vitamin d supplementation in obesity and during weight. Vitamin d, in its biologically active form calcitriol 1,25oh 2 d, plays an important role in calcium homeostasis, regulation of bone turnover, innate immune function, cell proliferation, and cell differentiation. In the hivinfected patients under treatment with efavirenz, vitamin d deficiency is prevalent. Excreted in bile metabolized to water soluble metabolites and then excreted in.
Vitamin d deficiency is common in youth with hiv1 infection in the united states 1, 2. Effects of cholecalciferol supplementation on serum and. Hiv linked to vitamin d deficiency verywell health. In addition, haart may impair vitamin d metabolism 15, 16 as shown by.
The effect of efavirenz on vitamin d metabolism is hypothesized to occur through the induction of 24hydroxylase, a cytochrome p450 enzyme, that inactivates 25ohd and 1,25ohd, similar to the effects of antiepileptics 24, 26, 27. The positive effects of vitamin d in different acute and chronic diseases e. All of these markers were measured in batch from archived frozen samples kept at. During monocytes and macrophages activation, the vdr and the enzyme 1. Efavirenz can cause worsening of underlying psychosis, mania, or insomnia, but has not been associated with higher rates of suicidality efavirenz affects vitamin d metabolism and thus 25oh vitamin d levels should be monitored while on efavirenz because levels may become dangerously elevated.
Methods treatmentnaive hiv patients with n102 or without n89 tuberculosis coinfection were enrolled prospectively. Journal of acquired immune deficiency syndromes 1999, 643, 279283. Effects of switching from efavirenz to raltegravir on endothelial function, bone mineral metabolism, inflammation, and renal function. Cholecalciferol is also available through diet via animal sources. Vitamin d deficiency is very high in hiv patients on antiretroviral therapy. Mar 29, 2016 vitamin d, which is important for calcium homeostasis and bone metabolism, has several noncalcemic actions. Current efavirenz use was positively associated with postrepletion. Finally, dilution in a large body volume and sequestration in adipose tissue were also proposed 10,16. Apr 21, 2016 as previous reports have indicated an increased risk of low bone mineral density and compromised vitamin d levels in patients treated with the antiretroviral drugs efavirenz and ritonavir, as well as with the glucocorticoid dexamethasone, it was of interest to study the effects of the drugs on the vitamin d 3 metabolism and mineralization in. Vitamin d 3 is made in the skin from 7dehydrocholesterol under the influence of uv light. S9 february 1998 with 1,107 reads how we measure reads. Dailymed symfi efavirenz, lamivudine and tenofovir. Moreover, the vitamin d activating enzyme cyp27b1 is also expressed in various immune cells, as well as intestinal epithelial cells 5, 6. Tdf administration disrupts vitamin d metabolism, 29,30 and the decrease in bmd associated with tdf initiation was attenuated in adults with coadministration of high doses of vitamin d3 4,000 international units iu daily and calcium carbonate 1,000 mg daily for the first 48 weeks of tdf treatment.
Effect of antiretrovirals on vitamin d clinical infectious. Adverse effects of antiretroviral medications question 620. Vitamin d is essential for regulating numerous biologic processes through the widespread distribution of its receptor and activating enzymes. The association of gender, age, efavirenz use, and. Sep 12, 2012 this study was not able to demonstrate a link between hyperparathyroidism and altered bone metabolism nor renal tubular dysfunction frequently seen in patients on tdf. The effect of efavirenz on vitamin d metabolism is hypothesized to occur through the induction of 24hydroxylase, a cytochrome p450 enzyme. Vitd plays a key role in the effector activity of innate immune cells in response to microbial infections. Current efavirenz use was positively associated with postrepletion 25ohd levels. Efavirenz, lamivudine and tenofovir disoproxil fumarate tablets is not recommended for patients with creatinine clearance less than 50 ml per min or patients with endstage renal disease esrd requiring hemodialysis because efavirenz, lamivudine and tenofovir disoproxil fumarate tabletsit is a fixeddose combination and the dosage of the. Effect of antiretrovirals on vitamin d clinical infectious diseases.
Calcidiol 25ohd, the circulating form of vitamin d and the best indicator of total body vitamin d, was measured in all patients in addition to the regular blood panel, which included renal, bone, liver and lipid profiles, full blood count, cd4 cell count, and hiv rna level. Vitamin metabolism vitamins are organic compounds that function as metabolic catalysts usually in the form of coenzymes smith 1970. Other studies have shown an increase in vitamin d level with switching from efavirenz to ritonavirboosted r atazanavir, a greater decrease with efavirenz than with rilpivirine. Pdf hiv infection and antiretroviral therapy art may create unique risk. Efavirenz reduces the expression of the cytochrome p450 enzyme cyp2r1 which is involved in converting vitamin d3 into 25 hydroxyvitamin d efavirenz upregulates cyp24 which converts active vitamin d to inactive metabolites. Serum glucose, creatinine, and cd4 cell count along. Excreted in bile metabolized to water soluble metabolites and then excreted in urine as well. While the reasons for this could be many, it is clear that hiv infection, in and of itself, contributes to this and that continued deficiency could have a negative impact on your longterm health. Adverse effects of antiretroviral medications question 620 hiv. Efavirenz is associated with severe vitamin d deficiency. Vitamin d is synthesized in the form of cholecalciferol vitamin d 3 in the epidermis upon exposure to ultraviolet light. In hivinfected persons, the safety of vitamin d supplementation has also. The effect of antiretrovirals on vitamin d pdf attached. Vitamin d deficiency and altered bone mineral metabolism in hiv.
Efavirenzcontaining cart regimens adversely affected vitamin d levels. Absorption vitamin d is absorbed from the small intestine for which bile is essential. After supplementation with single dose of 300,000 iu vitamin d in this population, the activation of osteoblasts and osteoclasts stimulates bone formation and resorption respectively with favorable bone formation without any adverse event. Vitamin and mineral requirements in human nutrition. Apr 14, 2020 tdf administration disrupts vitamin d metabolism, 29,30 and the decrease in bmd associated with tdf initiation was attenuated in adults with coadministration of high doses of vitamin d3 4,000 international units iu daily and calcium carbonate 1,000 mg daily for the first 48 weeks of tdf treatment. Once vitamin d deficiency is corrected, maintenance doses of 600 iu vitamin d daily are currently recommended by the iom for persons from 170 yr of age, although others recommend higher daily or monthly doses, and vitamin d 3 100,000 iu every 2 months has been used for chronic supplementation in children and youth with hiv infection. After changing the antiretroviral regimen from efavirenz boosted to ritonavirboosted saquinavir, the laboratory parameters began to normalize. Oct 16, 2014 absorption vitamin d is absorbed from the small intestine for which bile is essential. Distribution stored in adipose tissue metabolism transported to the liver, then kidneys, where it is activated 6. Klassen k, martineau ar, wilkinson rj, cooke g, courtney ap, et al. These forms of vitamin d, which are inert and have a short halflife, are converted in the liver via 25 hydroxylase to 25ohd 3, or calcidiol. Vitamin d is attributed to calcium and phosphate metabolism. Tenofovir df nucleoside and nucleotide analogue reverse. Vitamin d deficiency vdd has been associated with numerous adverse health outcomes, including rickets, osteomalacia, cardiovascular mortality, cancer, autoimmune.
Vitamins may be divided into a fatsoluble group a d e, and k and a watersoluble group the b complex and c. Vitamin d supplementation in obesity and during weight loss. However, few data from randomized, controlled trials exist. Oral route tablet severe acute exacerbations of hepatitis b virus hbv have been reported in patients who are coinfected with hiv1 and hbv and have discontinued products containing emtricitabine ftc andor tenofovir disoproxil fumarate tdf, which are components of efavirenz emtricitabine tenofovir disoproxil fumarate. Hiv infection and antiretroviral therapy art may create unique risk factors for vitamin d insufficiency, including alterations of vitamin d metabolism by art. Those serum levels are defined as deficiency of vitamin d. Vitamin d 2 ergocalciferol is derived from the plant sterol ergosterol. Change in vitamin d levels occurs early after antiretroviral therapy.
Vitamin d is an important nutrient for bone health, calcium balance, and immune function yet it is often found to be low in many people living with hiv. Thus, vitamin d is also critical for bone remodeling through its role as a potent stimulator of bone resorption. Vitamin d is metabolized first to 25 hydroxyvitamin d 25ohd, then to the hormonal form 1,25dihydroxyvitamin d 1,25oh 2 d. Treatment goal is to have a vitamin d level of at least 30 ngml, based on endocrine society practice guidelines 108, and may require supplementation with 2000 units of vitamin d daily. Efv induces the metabolism of vitamin d resulting in low vitd crosssectional study in cape town showed efv independently associated with lower bone mineral density medicine 2016 95. Symfi is a threedrug fixeddose combination product containing 600 mg of efavirenz efv, 300 mg of lamivudine 3tc, and 300 mg of tenofovir disoproxil fumarate tdf. Efavirenz efv, nevirapine nvp, tenofovir tdf and protease.
Vitamin d insufficiency is widespread in hivinfected patients. Recommendations for treatment of vitamin d deficiency all adults who are vitamin d deficient be treated with 50,000 iu of vitamin d2 or vitamin d3 once a week for 8 weeks followed by maintenance dose of 15002000 iuday of vitamin d3 obese adults, patients with malabsorption syndromes and patients on medications affecting vitamin d metabolism. The effect of antiretrovirals on vitamin d michael yin,1 and emily stein2 1division of infectious diseases and 2 division of endocrinology, columbia university medical center, new york, new york see the article by dao et al, on pages 396405. While the causes of vitamin d deficiency in hiv are multifactorial, including inadequate diet and darker skin pigmentation, certain. D has wellknown regulatory functions in calcium metabolism, but is. Low vitamin d levels have been observed in hivinfected patients from high latitudes, with consequently reduced bone mineral density bmd, but data from the tropics are scarce. Frontiers the potential protective role of vitamin d.
Recommendations for correction of vitamin d deficiency vary widely 312, but vitamin d 2 or d 3 50,000 iu weekly for 5 to 8 weeks is commonly recommended. However, the exact mechanism and whether 24hydroxylase activity is attenuated over time have not been established. The effect of tenofovir on vitamin d metabolism in hiv. Vitamin d deficiency can result in lower bone mineral density and an increased risk of reduced bone density osteoporosis or bone fracture because a lack of vitamin d alters mineral metabolism in the body. The antiretroviral drugs efavirenz and ritonavir as well as the. Decrease of vitamin d concentration in patients with hiv infection on. Urinary calcium excretion was significantly lower in all patients on tdf. Hiv andor antiretroviral therapy art, particularly efavirenz efv, may interfere with vitamin d metabolism. Effects of vitamin d supplementation on the bone specific. In a multivariate model that included all 1077 patients, sampling in winter, black ethnicity, nadir cd4 cell count less than 200 cells. Vitamin d deficiency appeared to be overriding the effect of tdf on 1. These two vital players of vitamin d metabolism have also been colocalized in different cells of the gi tract suggesting the need for active vitamin d in those cells 7. High prevalence of vitamin d deficiency in hiv infected on.
Distribution of patients according to their 25oh d serum level. We have not found any study that evaluated effects of vitamin d supplementation on the bone specific biomarkers in hiv positive patients under treatment with antiretroviral regimen containing efavirenz. The largest group is that of patients with 25 oh d level between 1030 ngml 73 % n105. Effects of switching from efavirenz to raltegravir on endothelial function, bone mineral metabolism. The local metabolism of vitamin d and its role in bone has been. Vitamin d metabolism, mechanism of action, and clinical. Efavirenz, lamivudine and tenofovir fda prescribing. Vitamin d metabolism and action article pdf available in osteoporosis international 8 suppl 2s2. Vitamin d status also modified the effects of tenofovir on serum concentrations of 1,25oh 2d and phosphate. It was reported that antiretroviral drugs such as efavirenz can increase the catabolism of vitamin d in hiv infected individuals. Vitamin d, bone, and hiv infection pubmed central pmc.