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Vitamin D Deficiency Prevalence and Associations
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Reported by Jules Levin
CROI 2010 Feb 16-19 SF
Assessment of Vitamin D Levels among HIV-infected Persons in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study): 71.6% (95% confidence interval [CI] 68.1 to 74.9) were 25(OH)D insufficient.
Christine Dao1, P Patel1, S Pals1, T Bush1, F Rhame2, T Overton3, E Kojic4, K Wood5, J Brooks1, and the SUN Study Investigators
1CDC, Atlanta, GA, US; 2Abbott-Northwestern Hosp, Minneapolis, MN, US; 3Washington Univ in St Louis, Sch of Med, MO, US; 4The Miriam Hosp, Providence, RI, US; and 5Cerner Corp, Vienna, VA, US
Background: Vitamin D insufficiency as assessed by levels of serum 25-hydroxyvitamin D (25[OH]D), which is activated and converted to 1,25-dihydroxyvitamin D (1,25[OH]D) in the kidneys, is highly prevalent in the general U.S. adult population and has been associated with many chronic illnesses that commonly affect persons with HIV. Like anti-epileptics, efavirenz may induce hepatic catabolism of 25(OH)D via the cytochrome P450 system resulting in vitamin D insufficiency. We explored 25(OH)D levels and associated factors for insufficiency in an adult HIV cohort.
Methods: We examined baseline data from the SUN Study, a prospective observational cohort of 700 HIV-infected adults enrolled at clinics in 4 U.S. cities from March 2004-June 2006. We reviewed behavioral, clinical (including bone mineral density [BMD]), and laboratory data (including 25(OH)D), and estimated ultraviolet (UV) exposure from National Weather Service data. Using multivariable logistic regression, we examined risk factors for 25(OH)D insufficiency defined as <30 ng/mL.
Results: Among 672 participants with baseline serum 25(OH)D determinations who were not receiving vitamin D supplements (median age 41 years, 77% male, 30% black and 10% Hispanic, median CD4 count 471 cells/mm3, 74% with HIV RNA viral loads <400 copies/mL), 71.6% (95% confidence interval [CI] 68.1 to 74.9) were 25(OH)D insufficient. In multivariable analysis, black race (adjusted odds ratio [aOR] = 4.50, 95%CI 2.59 to 7.85), Hispanic ethnicity (aOR = 2.78, 95%CI 1.31 to 5.90), lower UV exposure (aOR = 1.28, 95%CI 1.17 to 1.40), hypertension (aOR = 1.88, 95%CI 1.10 to 3.22), lack of exercise (aOR = 3.14, 95%CI 1.80 to 5.47), and efavirenz exposure (aOR = 1.98, 95%CI 1.18 to 3.34) were independently associated with 25(OH)D insufficiency. Renal insufficiency (aOR for GFR <90 mL/min/1.73m2 = 0.55, 95%CI 0.36 to 0.83) and ritonavir exposure (aOR = 0.56, 95%CI 0.35 to 0.89) were associated with lower odds of 25(OH)D insufficiency. We observed no association between 25(OH)D insufficiency and gender, age, or BMD.
Conclusions: Nearly three-fourths of HIV-infected adults in this contemporary cohort were 25(OH)D insufficient. The observed associations of 25(OH)D insufficiency with renal insufficiency, and with ritonavir and efavirenz exposures are consistent with both HIV-related and therapy-mediated alterations in vitamin D metabolism. Calcium and vitamin D supplementation to prevent osteomalacia might be warranted for persons using efavirenz.
Prevalence of Hypovitaminosis D among HIV+ Patients Enrolled in a Large Italian Cohort: VitD insufficiency and deficiency were found in 807 (54%) and 98 (7%) of the tests.....high negative impact of hypD on risk of morbidity in this population should be carefully taken into account.
Marco Borderi1, F Vescini2, A Cozzi-Lepri3, A Di Caro4, I Shlacht5, G Cassola6, G Pellizzer7, J Vecchiet8, M C Re9, A d’Arminio Monforte10, and for the Icona Fndn Study Group
1S Orsola Hosp, Bologna, Italy; 2Gorizia Central Hosp, Italy; 3Royal Free and Univ Coll London Med Sch, UK; 4INMI L Spallanzani, Rome, Italy; 5Hosp Niguarda Ca Granda, Milan, Italy; 6San Martino Hosp, Genoa, Italy; 7San Bortolo Hosp, Vicenza, Italy; 8Infectious Disease Clin, Chieti, Italy; 9Univ of Bologna, Italy; and 10San Paolo Hosp, Univ of Milan, Italy
Background: Hypovitaminosis D (hypD) is a frequent condition in industrialized countries and is associated with several pathological states. A high prevalence of hypD in HIV+ patients has been reported, but the reasons are unclear. The aim of this study is to estimate the prevalence of hypD in a cohort of HIV+ patients before and after start of combination antiretroviral therapy (cART), and its association with anthropometric, environmental, and clinical data.
Methods: Patients of the ICONA cohort, for whom a stored plasma sample was available before and after starting cART, were used for dosing 25(OH)-vitaminD (vitD) concentration; all data used were recorded at blood collection. VitD insufficiency defined as 25(OH)-vitD <75 nmol/L, values <30 nmol/L considered vitD deficiency. Differences in the proportion of patients with insufficiency were tested by chi-square test and logistic regression analysis accounting for non independence of tests. The change in absolute levels of vitD pre/post cART was modelled by linear regression controlling for confounders and seasonality (only pairs of tests measured in the same season included).
Results: We studied 856 patients contributing 1,505 tests: 262 before and 1,243 after a median of 14 months (IQR: 8 to 19) of ART (369 non-nucleoside reverse transcriptase inhibitor-based and 874 protease inhibitor-based regimens). Median age 36 years (IQR: 20 to 69); 800 (93%) were from Italy, 11 (1%) from Europe, 23 (3%) from Africa, 18 (2%) from Central/South America, 4 (0.5%) from Asia. VitD insufficiency and deficiency were found in 807 (54%) and 98 (7%) of the tests.
In multivariable analysis, only age (OR = 1.35 per 10 years older, 95%CI 1.2 to 1.6, P =0.0001), Western-world nationality (OR = 0.35 vs African, Asian, or Centre/South American, 95%CI 0.2 to 0.6, P =0.0001) and duration of ART (OR = 1.33 per year longer, 95%CI 1.1 to 1.5, P =0.0001) were independently associated with vitD insufficiency risk . There was no evidence from the linear regression model that change in vitD levels from pre-ART to post ART varied according to whether patients were receiving protease inhibitors vs non-nucleoside reverse transcriptase inhibitors (mean difference/year = +15 nmol/L, 95% CI -6 to +36, P =0.17).
Conclusions: This is the first large study confirming a very high prevalence of hypD in HIV+ patients, much more frequent than in the general population. These data should carefully considered in the clinical management of HIV+ patients, cause our patients were very much younger that HIV‑ case series reported in the literature, and high negative impact of hypD on risk of morbidity in this population should be carefully taken into account.
High Prevalence of Severe Vitamin D Deficiency in cART Naïve and Successfully Treated Swiss HIV Patients: systematic screening with consideration of seasonality is warranted.
N Mueller1, Christoph Fux2, B Ledergerber1, L Elzi3, P Schmid4, T Dang5, L Magenta6, A Calmy7, A Vergopoulos1, H Bischoff-Ferrari1, and Swiss HIV Cohort Study
1Univ Hosp Zurich, Switzerland; 2Univ Hosp Bern, Switzerland; 3Univ Hosp Basel, Switzerland; 4Cantonal Hosp, St Gallen, Switzerland; 5Ctr Hosp Univ Vaudois, Lausanne, Switzerland; 6Ospedale Civico di Lugano, Switzerland; and 7Univ Hosp Geneva, Switzerland
Background: To evaluate the prevalence of 25-hydroxy vitamin D [25(OH)D] deficiency in HIV+ patients, a population at risk for osteoporosis.
Methods: Retrospective assessment of serum vitamin D levels within the Swiss HIV Cohort Study by season (spring vs fall) and initiation of combined antiretroviral treatment (cART). 25(OH)D was measured in 211 HIV+ patients (75% men, 88% Caucasian, median age 37 years) at 3 consecutive time points: The first sample was taken before initiation of cART, either from Feb to Apr or from Aug to Oct. Samples 2 and 3 were taken after starting cART at 12 (same season) and 18 months (alternate season) after the first sample. 1,25(OH)2D was measured in a subset of 74 patients. Multivariable analyses included season, gender, age, ethnicity, body mass index, IDU, renal function, duration since HIV diagnosis, previous AIDS, CD4 cell count, and cART, in particular protease inhibitors vs non-nucleoside reverse transcriptase inhibitor (NNRTI), as well as tenofovir disoproxil fumarate (TDF)-use.
Results: At baseline, median 25(OH)D levels were 36.5 (IQR 20.1 to 49.3) nmol/L in spring and 57.4 (38.8 to 74.1) nmol/L in the fall; 25(OH)D deficiency <30 nmol/L was more prevalent in spring (42%) than in fall (14%), but remained unchanged after cART initiation. Multivariable analysis demonstrated a positive correlation of 25(OH)D levels with Caucasian ethnicity and duration since HIV diagnosis, as well as a negative correlation with IVDU and NNRTI-use. 1-Hydroxylation rates were significantly higher in patients with low 25(OH)D. IVDU, previous AIDS, and higher CD4 counts correlated with lower 1,25(OH)2D; BMI, and TDF-use with higher 1,25(OH)2D levels. In TDF-treated patients, higher 1,25(OH)2D correlated with increases in serum alkaline phosphatase.
Conclusions: Based on the high rate of vitamin D deficiency in HIV-positive patients systematic screening with consideration of seasonality is warranted. The impact of NNRTI on 25(OH)D and TDF on 1,25(OH)2D needs further attention.
Vitamin D Deficiency and Bacterial Vaginosis among HIV-infected and -uninfected Women in the United States
Audrey French1,2, O Adeyemi1,2, D Agniel2, M Yin3, K Anastos4, and M Cohen1,2
1Rush Univ Med Ctr, Chicago, IL, US; 2CORE Ctr, Stroger Hosp of Cook County, Chicago, IL, US; 3Columbia Univ Med Ctr, New York, NY, US; and4Montefiore Med Ctr, Bronx, NY, US
Background: Bacterial vaginosis (BV), the most frequent cause of vaginitis, is associated with morbidities such as premature labor and increased susceptibility to HIV. Recently an association between vitamin D deficiency (VDD) and BV was identified in pregnant women. We sought to replicate this finding in the Women’s Interagency HIV Study (WIHS).
Method: A cross-sectional study of women participating in the WIHS, a longitudinal study of women with and at risk for HIV. Women in this substudy were from Chicago or New York. BV was defined by the Amsel criteria. VDD was defined as 25 (OH) D ≤20 ng/mL and insufficiency as >20 and ≤30 ng/mL.
Results: Among 609 women studied (6 of whom were pregnant), BV was found in 19% (table). VDD was found in 60% and insufficiency in 23.5%. VDD was associated with black race, 268 of 397 vs 59 of 92 for whites, OR 3.16 (95%CI, 2.06 to 4.89), but not with HIV status, CD4, or age. Vitamin D level strongly correlated with BV (r= -0.14, P <0.001) and there was a dose response relationship; BV was most likely in women with VDD (OR 3.55), then women with insufficient levels (OR 2.12) compared with sufficient vitamin D. In multivariate analysis black race, AOR 6.03, VDD, AOR 2.46, and number of sex partners, AOR 1.54, were independently associated with BV.
Conclusions: In this study of 609 HIV-infected and -uninfected women, BV and VDD were common and significantly correlated. VDD may partially explain the relationship between black race and BV and may be a modifiable risk factor for the disorder. Further study is needed to determine whether repletion of vitamin D will decrease the occurrence of BV.
*OR for linear increase
Vitamin D and HIV-related Complications and HIV Disease Progression in Women in Tanzania
Saurabh Mehta1, D Spiegelman1, F Mugusi2, E Giovannucci1, G Msamanga2, and W Fawzi1
1Harvard Sch of Publ Hlth, Boston, MA, US and 2Muhimbili Univ of Hlth and Allied Sci, Dar es Salaam, Tanzania
Background: Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune function. However, this relationship has not been examined in large studies or in resource-limited settings.
Methods: Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV disease progression and related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes.
Results: Women with low vitamin D status (serum 25-hydroxyvitamin D <32 ng/mL) had 45% higher risk of reaching a body mass index <18 kg/m2 during the first 2 years of follow-up, compared to women with adequate vitamin D levels (incidence rate ratio, RR: 1.45; 95%CI 1.04 to 2.01). The relationship between continuous vitamin D levels and risk of body mass index <18 kg/m2 during follow-up was inverse and linear (P=0.03; Figure 1). Low vitamin D status was associated with a 25% higher risk of progression to WHO HIV disease stage III or IV during follow-up (RR: 1.25; 1.05 to 1.50), compared to adequate vitamin D status. This risk decreased with increasing vitamin D levels linearly (P =0.05; Figure 2). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (RR: 1.28, 1.05 to 1.55) and thrush (RR: 2.92, 1.43 to 5.96) diagnosed during the first 2 years of follow-up. Women in the lowest vitamin D quintiles had higher incidence of mouth and throat ulcers, painful tongue or mouth, difficult or painful swallowing, diarrhea, and fatigue during the first 2 years of follow-up.
Conclusions: Vitamin D status has a protective association with HIV disease progression and HIV-related complications during follow-up in HIV-infected women. If confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to prolong the time to ART initiation in HIV-infected patients and improve health and quality of life, particularly in resource-limited settings.
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