Effects of Vitamin D Supplementation on Bone Health and Bone-related Parameters in HIV-infected Patients: A Systematic Review and Meta-analysis.

PURPOSE: There is growing evidence that bone health is decreased in individuals with HIV infection. Vitamin D deficiency is also highly prevalent among HIV-infected patients. The literature was systematically reviewed to determine whether bone health and bone-related parameters may improve with vitamin D supplementation in HIV-infected individuals. METHODS: Four databases were systematically searched for randomized clinical trials of vitamin D supplementation in HIV infection, published from January 1990 to September 2021. No language or publication restrictions were applied. Standardized mean differences (SMD) with 95% CIs are reported. A random-effects model was used to perform meta-analysis. FINDINGS: Ten studies met the inclusion criteria (N = 733 participants at study completion). The mean ages of the patients in the included trials ranged from 10 to 49 years. The meta-analysis indicated that with vitamin D supplementation, serum 25-hydroxy vitamin D (25[OH]D) level was significantly increased (SMD, 1.86; 95% CI, 1.02 to 2.70; I2 = 94.4%), but there were no significant effects on levels of serum 1,25-dihydroxy vitamin D (1,25-[OH]2D) (SMD, 0.29; 95% CI, -0.07 to 0.64; I2 = 67.4%), total bone mineral density (SMD, 0.07; 95% CI, -0.23 to 0.37; I2 = 00.0%), spine bone mineral density (SMD, 0.15; 95% CI, -0.19 to 0.49; I2 = 17.3%), and parathyroid hormone level (SMD, -0.18; 95% CI, -0.37 to 0.02; I2 = 1.2%) in HIV-infected patients. IMPLICATIONS: This study showed that vitamin D supplementation can improve serum 25(OH)D in HIV-infected patients. The effects of vitamin D supplementation on other bone health-related parameters such as bone mineral density and parathyroid hormone in HIV-infected patients need to be further investigated in larger-scale, well-designed randomized, controlled trials.

Prevalence and Clinical Outcomes of Vitamin D Deficiency in COVID-19 Hospitalized Patients: A Retrospective Single-Center Analysis.

Vitamin D attenuates inflammatory responses to viral respiratory infections. Hence, vitamin D deficiency may be a highly significant prognostic factor for severity and mortality in COVID-19 patients. To evaluate the complications and mortality in different vitamin D status groups in COVID-19 hospitalized patients, we conducted this retrospective study on 646 laboratory-confirmed COVID-19 patients who were hospitalized in Shahid Modarres Hospital, Tehran, Iran from 16th March 2020 until 25th February 2021. Overall, patients with vitamin D deficiency, insufficiency and sufficiency were 16.9%, 43.6% and 39.5%, respectively. The presence of comorbidity, length of hospitalization, ICU admission, and invasive mechanical ventilation requirement and overall complications were significantly more in patients with vitamin D deficiency (p-value < 0.001). 46.8% (51/109) of vitamin D deficient patients died due to the disease, whilst the mortality rate among insufficient and sufficient vitamin D groups was 29.4% (83/282) and 5.5% (14/255), respectively. In univariate analysis, age > 60 years (odds ratio (OR) = 6.1), presence of comorbidity (OR = 10.7), insufficient vitamin D status (OR = 7.2), and deficient vitamin D status (OR = 15.1) were associated with increase in COVID-19 mortality (p-value < 0.001). Finally, the multivariate analysis adjusted for age, sex, and comorbidities indicated vitamin D deficiency as an independent risk factor for mortality (OR = 3.3, p-value = 0.002). Vitamin D deficiency is a strong risk factor for mortality and severity of SARS-CoV-2 infection. Vitamin D supplementation may be able to prevent or improve the prognosis of COVID-19 during this pandemic.

Impact of vitamin D on the course of COVID-19 during pregnancy: A case control study.

OBJECTIVE: We aimed to evaluate the vitamin D status of pregnant women with COVID-19, and the association between vitamin D level and severity of COVID-19. METHODS: In this case control study, 159 women with a single pregnancy and tested positive for SARS-CoV-2, and randomly selected 332 healthy pregnant women with similar gestational ages were included. COVID-19 patients were classified as mild, moderate, and severe. Vitamin D deficiency was defined as 25-hydroxycholecalciferol <20 ng/mL (50 nmol/L), and 25-OH D vitamin <10 ng/mL was defined as severe vitamin D deficiency, also 25-OH D vitamin level between 20-29 ng/mL (525-725 nmol/L) was defined as vitamin D insufficiency. RESULTS: Vitamin D levels of the pregnant women in the COVID-19 group (12.46) were lower than the control group (18.76). 25-OH D vitamin levels of those in the mild COVID-19 category (13.69) were significantly higher than those in the moderate/severe category (9.06). In terms of taking vitamin D supplementation, there was no statistically significant difference between the groups. However, it was observed that all of those who had severe COVID-19 were the patients who did not take vitamin D supplementation. CONCLUSION: The vitamin D levels are low in pregnant women with COVID-19. Also, there is a significant difference regarding to vitamin D level and COVID-19 severity in pregnant women. Maintenance of adequate vitamin D level can be useful as an approach for the prevention of an aggressive course of the inflammation induced by this novel coronavirus in pregnant women.

Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study.

BACKGROUND: The objective of this extension phase of the quasi-experimental GERIA-COVID study was to determine whether vitamin D3 supplementation taken prior to or during COVID-19 was associated with better 3-month survival in geriatric patients hospitalized for COVID-19. METHODS: Intervention group was defined as all participants supplemented with vitamin D3 prior to or during COVID-19 (n = 67). Supplements were either bolus vitamin D3 (ie, 50,000 IU per month, or 80,000 IU or 100,000 IU or 200,000 IU every 2-3 months), or daily supplementation with 800 IU. Comparator group involved those without vitamin D supplements (n = 28). Outcome was 3-month mortality. Covariables were age, sex, functional abilities, history of malignancies, cardiomyopathy, undernutrition, number of acute health issues, antibiotics use, systemic corticosteroids use, and 25(OH)D concentration. RESULTS: 76.1 % (n = 51) of participants survived at 3 months in Intervention group, compared to only 53.6 % (n = 15) in Comparator group (P = 0.03). The fully-adjusted hazard ratio for 3-month mortality was HR = 0.23 [95 %CI: 0.09;0.58](P = 0.002) in Intervention group compared to Comparator group. Intervention group had also longer survival time (log-rank P = 0.008). CONCLUSIONS: Vitamin D3 supplementation was associated with better 3-month survival in older COVID-19 patients.

The Impact of Vitamin D Level on COVID-19 Infection: Systematic Review and Meta-Analysis.

Background: Coronavirus disease (COVID-19) is a respiratory and systemic disorder caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or novel Coronavirus (nCoV). To date, there is no proven curative treatment for this virus; as a result, prevention remains to be the best strategy to combat coronavirus infection (COVID-19). Vitamin D deficiency (VDD) has been proposed to play a role in coronavirus infection (COVID-19). However, there is no conclusive evidence on its impact on COVID-19 infection. Therefore, the present review aimed to summarize the available evidence regarding the association between Vitamin D levels and the risk of COVID-19 infection. Methods: A systematic literature search of databases (PUBMED/MEDLINE, Cochrane/Wiley library, Scopus, and SciELO) were conducted from May 15, 2020, to December 20, 2020. Studies that assessed the effect of vitamin D level on COVID-19/SARS-2 infection were considered for the review. The qualities of the included studies were evaluated using the JBI tools. Meta-analysis with a random-effects model was conducted and odds ratio with their 95%CI were reported. This systematic review and meta-analysis are reported according to the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline. Results: The electronic and supplementary searches for this review yielded 318 records from which, only 14 of them met the inclusion criteria. The qualitative synthesis indicated that vitamin D deficient individuals were at higher risk of COVID-19 infection as compared to vitamin D sufficient patients. The pooled analysis showed that individuals with Vitamin-D deficiency were 80% more likely to acquire COVID-19 infection as compared to those who have sufficient Vitamin D levels (OR = 1.80; 95%CI: 1.72, 1.88). Begg's test also revealed that there was no significant publication bias between the studies (P = 0.764). The subgroup analysis revealed that the risk of acquiring COVID-19 infection was relatively higher in the case-control study design (OR = 1.81). Conclusions: In conclusion, low serum 25 (OH) Vitamin-D level was significantly associated with a higher risk of COVID-19 infection. The limited currently available data suggest that sufficient Vitamin D level in serum is associated with a significantly decreased risk of COVID-19 infection.

Role of vitamin D in treating COVID-19-associated coagulopathy: problems and perspectives.

Aggressive inflammatory response leading to hypercoagulability has been found to be associated with disease severity in COVID-19 patients and portends bad treatment outcome. A state of acute disseminated intravascular coagulation (DIC), along with pulmonary embolism and/or deep vein thrombosis, has been observed in critically ill ICU patients. Autopsy reports of COVID-19 patients demonstrated microthrombi in lungs and in other organs, as well as marked inflammatory changes, characteristic clinicopathological features that exacerbate disease severity. Vitamin D supplementation was recommended by many clinicians across the globe to improve clinical symptoms of COVID-19 patients, mainly because of its immunomodulatory roles on immune cells. Furthermore, vitamin D and its associated molecules are also known to directly or indirectly regulate various thrombotic pathways. We propose that vitamin D supplementation not only attenuates the risk of Acute Respiratory Disease Syndrome (ARDS) but it also may have a role in reducing coagulation abnormalities in critically ill COVID-19 patients. The overarching goal of this review is to discuss the effects of vitamin D on coagulation pathways and other intertwined processes leading to thrombosis. Many clinical trials are currently investigating the efficacy of vitamin D supplementation in reducing the risk of COVID-19 infection. However, randomized placebo control clinical trials are also necessary to ascertain the effect of vitamin D supplementation on reducing the risk of coagulopathy in COVID-19 patients.

l-Cysteine Stimulates the Effect of Vitamin D on Inhibition of Oxidative Stress, IL-8, and MCP-1 Secretion in High Glucose Treated Monocytes.

Objective: Vitamin D deficiency is common in the general population and diabetic patients, and supplementation with vitamin D is widely used to help lower oxidative stress and inflammation. The cytokine storm in SARS-CoV2 infection has been linked with both diabetes and Vitamin D deficiency. This study examined the hypothesis that supplementation with vitamin D, in combination with l-cysteine (LC), is better at reducing oxidative stress and thereby, more effective, at inhibiting the secretion of the pro-inflammatory cytokines, Interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in U937 monocytes exposed to high glucose concentrations. Methods: U937 monocytes were pretreated with 1,25 (OH)2 vitamin D (VD, 10 nM) or LC (250 µM) or VD + LC for 24 h and then exposed to control or high glucose (HG, 25 mM) for another 24 h. Results: There were significantly greater reactive oxygen species (ROS) levels in monocytes treated with HG than those in controls. Combined supplementation with VD and LC showed a more significant reduction in ROS (46%) in comparison with treatment with LC (19%) or VD (26%) alone in monocytes exposed to HG. Similarly, VD supplementation, together with LC, caused a more significant inhibition in the secretion of IL-8 (36% versus 16%) and MCP-1 (46% versus 26%) in comparison with that of VD (10 nM) alone in high-glucose treated monocytes. Conclusions: These results suggest that combined supplementation with vitamin D and LC has the potential to be more effective than either VD or LC alone in lowering the risk of oxidative stress and inflammation associated with type 2 diabetes or COVID-19 infection. Further, this combined vitamin D with LC/N-acetylcysteine may be a potent alternative therapy for SARS-CoV2 infected subjects. This approach can prevent cellular damage due to cytokine storm in comorbid systemic inflammatory conditions, such as diabetes, obesity, and hypertension.

Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19.

BACKGROUND: The severity of Coronavirus Disease 2019 (COVID-19) is a multifactorial condition. An increasing body of evidence argues for a direct implication of vitamin D deficiency, low serum calcium on poor outcomes in COVID-19 patients. This study was designed to investigate the relationship between these two factors and COVID-19 in-hospital mortality. MATERIALS: This is a prospective study, including 120 severe cases of COVID-19, admitted at the department of Reanimation-Anesthesia. Vitamin D was assessed by an immuno-fluoroassay method. Total serum calcium by a colorimetric method, then, corrected for serum albumin levels. The association with in-hospital mortality was assessed using the Kaplan-Meier survival curve, proportional Cox regression analyses and the receiver operating characteristic curve. RESULTS: Hypovitaminosis D and hypocalcemia were very common, occurring in 75% and 35.8% of patients. When analyzing survival, both were significantly associated with in-hospital mortality in a dose-effect manner (pLog-Rank = 0.009 and 0.001 respectively). A cutoff value of 39 nmol/l for vitamin D and 2.05 mmol/l for corrected calcemia could predict poor prognosis with a sensitivity of 76% and 84%, and a specificity of 69% and 60% respectively. Hazard ratios were (HR = 6.9, 95% CI [2.0-24.1], p = 0.002 and HR = 6.2, 95% CI [2.1-18.3], p = 0.001) respectively. CONCLUSION: This study demonstrates the high frequency of hypocalcemia and hypovitaminosis D in severe COVID-19 patients and provides further evidence of their potential link to poor short-term prognosis. It is, therefore, possible that the correction of hypocalcemia, as well as supplementation with vitamin D, may improve the vital prognosis.

Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity.

Vitamin D deficiency co-exists in patients with COVID-19. At this time, dark skin color, increased age, the presence of pre-existing illnesses and vitamin D deficiency are features of severe COVID disease. Of these, only vitamin D deficiency is modifiable. Through its interactions with a multitude of cells, vitamin D may have several ways to reduce the risk of acute respiratory tract infections and COVID-19: reducing the survival and replication of viruses, reducing risk of inflammatory cytokine production, increasing angiotensin-converting enzyme 2 concentrations, and maintaining endothelial integrity. Fourteen observational studies offer evidence that serum 25-hydroxyvitamin D concentrations are inversely correlated with the incidence or severity of COVID-19. The evidence to date generally satisfies Hill's criteria for causality in a biological system, namely, strength of association, consistency, temporality, biological gradient, plausibility (e.g., mechanisms), and coherence, although experimental verification is lacking. Thus, the evidence seems strong enough that people and physicians can use or recommend vitamin D supplements to prevent or treat COVID-19 in light of their safety and wide therapeutic window. In view of public health policy, however, results of large-scale vitamin D randomized controlled trials are required and are currently in progress.

Vitamin D Deficiency and Outcome of COVID-19 Patients.

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses an enormous challenge to health care systems throughout the world. Without causal treatment, identification of modifiable prognostic factors may help to improve outcomes. To explore possible associations of vitamin D (VitD) status with disease severity and survival, we studied 185 patients diagnosed with coronavirus disease 2019 (COVID-19) and treated at our center. VitD status at first presentation was assessed retrospectively using accredited laboratory methods. VitD deficiency was defined as serum total 25-hydroxyvitamin D level < 12 ng/mL (<30 nM). Primary endpoint was severe course of disease (i.e., need for invasive mechanical ventilation and/or death, IMV/D). Within a median observation period of 66 days (range 2-92), 23 patients required IMV. A total of 28 patients had IMV/D, including 16 deaths. Ninety-three (50%) patients required hospitalization (inpatient subgroup). A total of 41 (22%) patients were VitD deficient. When adjusted for age, gender, and comorbidities, VitD deficiency was associated with higher risk of IMV/D and death (HR 6.12, 95% CI 2.79-13.42, p < 0.001 and HR 14.73, 95% CI 4.16-52.19, p < 0.001, respectively). Similar correlations were observed in the inpatient subgroup. Our study demonstrates an association between VitD deficiency and severity/mortality of COVID-19, highlighting the need for interventional studies on VitD supplementation in SARS-CoV-2 infected individuals.

Immune Modulatory Effects of Vitamin D on Viral Infections.

Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D's antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections.

Impact of Vitamin D Deficiency on COVID-19-A Prospective Analysis from the CovILD Registry.

The novel Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a global health concern. Vitamin D (VITD) deficiency has been suggested to alter SARS-CoV-2 susceptibility and the course of disease. Thus, we aimed to investigate associations of VITD status to disease presentation within the CovILD registry. This prospective, multicenter, observational study on long-term sequelae includes patients with COVID-19 after hospitalization or outpatients with persistent symptoms. Eight weeks after PCR confirmed diagnosis, a detailed questionnaire, a clinical examination, and laboratory testing, including VITD status, were evaluated. Furthermore, available laboratory specimens close to hospital admission were used to retrospectively analyze 25-hydroxyvitamin D levels at disease onset. A total of 109 patients were included in the analysis (60% males, 40% females), aged 58 ± 14 years. Eight weeks after the onset of COVID-19, a high proportion of patients presented with impaired VITD metabolism and elevated parathyroid hormone (PTH) levels. PTH concentrations were increased in patients who needed intensive care unit (ICU) treatment, while VITD levels were not significantly different between disease severity groups. Low VITD levels at disease onset or at eight-week follow-up were not related to persistent symptom burden, lung function impairment, ongoing inflammation, or more severe CT abnormalities. VITD deficiency is frequent among COVID-19 patients but not associated with disease outcomes. However, individuals with severe disease display a disturbed parathyroid-vitamin-D axis within their recovery phase. The proposed significance of VITD supplementation in the clinical management of COVID-19 remains elusive.

The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has led to a declaration of a Public Health Emergency of International Concern by the World Health Organization. As of May 18, 2020, there have been more than 4.7 million cases and over 316,000 deaths worldwide. COVID-19 is caused by a highly infectious novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to an acute infectious disease with mild-to-severe clinical symptoms such as flu-like symptoms, fever, headache, dry cough, muscle pain, loss of smell and taste, increased shortness of breath, bilateral viral pneumonia, conjunctivitis, acute respiratory distress syndromes, respiratory failure, cytokine release syndrome (CRS), sepsis, etc. While physicians and scientists have yet to discover a treatment, it is imperative that we urgently address 2 questions: how to prevent infection in immunologically naive individuals and how to treat severe symptoms such as CRS, acute respiratory failure, and the loss of somatosensation. Previous studies from the 1918 influenza pandemic have suggested vitamin D's non-classical role in reducing lethal pneumonia and case fatality rates. Recent clinical trials also reported that vitamin D supplementation can reduce incidence of acute respiratory infection and the severity of respiratory tract diseases in adults and children. According to our literature search, there are no similar findings of clinical trials that have been published as of July 1st, 2020, in relation to the supplementation of vitamin D in the potential prevention and treatment for COVID-19. In this review, we summarize the potential role of vitamin D extra-renal metabolism in the prevention and treatment of the SARS-CoV-2 infection, helping to bring us slightly closer to fulfilling that goal. We will focus on 3 major topics here: 1. Vitamin D might aid in preventing SARS-CoV-2 infection: Vitamin D: Overview of Renal and Extra-renal metabolism and regulation. Vitamin D: Overview of molecular mechanism and multifaceted functions beyond skeletal homeostasis. Vitamin D: Overview of local immunomodulation in human infectious diseases. Anti-viral infection. Anti-malaria and anti-systemic lupus erythematosus (SLE). 2. Vitamin D might act as a strong immunosuppressant inhibiting cytokine release syndrome in COVID-19: Vitamin D: Suppression of key pro-inflammatory pathways including nuclear factor kappa B (NF-kB), interleukin-6 (IL-6), and tumor necrosis factor (TNF). 3. Vitamin D might prevent loss of neural sensation in COVID-19 by stimulating expression of neurotrophins like Nerve Growth Factor (NGF): Vitamin D: Induction of key neurotrophic factors. .

COVID-19 fatalities, latitude, sunlight, and vitamin D.

BACKGROUND: Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. METHODS: Eighty-eight countries were selected based on their likelihood of providing reliable data. Using death rates/million for each country from the "worldometer" website, a correlation analysis was done between death rates and a country's latitude. RESULTS: A highly significant, positive correlation was found between lower death rates and a country's proximity to the equator (Pearson r = 0.40 P < .0001, 2-tailed t test). The R squared of 0.16 means that 16% of the variation in death rates among nations is accounted for by the latitude of the country. Evidence is presented suggesting a direct correlation between sunlight exposure and reduced mortality. DISCUSSION: This study is the first to document a statistically significant correlation between a country's latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Limitations of this study are noted. CONCLUSIONS: Further research is needed to confirm the correlation between latitude and COVID-19 fatalities, and to determine the optimum amounts of safe sunlight exposure and/or vitamin D oral supplementation to reduce COVID-19 fatalities in populations that are at high risk for vitamin D deficiency.

Maternal plasma vitamin D levels and associated determinants in late pregnancy in Harare, Zimbabwe: a cross-sectional study.

BACKGROUND: The importance of vitamin D in bone health and calcium homeostasis has been well documented. However, emerging evidence supports the role of vitamin D beyond its recognised traditional roles. In pregnancy, vitamin D levels are crucial in sustaining both the maternal stores and optimal growth of the foetus. In Southern Africa, there is paucity of data on vitamin D in pregnancy and related outcomes. To expand this body of knowledge, we assessed vitamin D levels in late pregnancy and (if any) associated maternal determinants in Harare, Zimbabwe. METHODS: Study participants comprised of 138 pregnant Zimbabwean women in their third trimester. These were stratified by HIV status; sampling median (IQR) gestation for HIV negative study participants was 34 weeks (26-41) and 31 weeks (20-40) in the HIV positive participants. Maternal plasma 25 hydroxyvitamin (OH) Dlevels were measured using the ClinPrepHigh Pressure Liquid Chromatography (HPLC) kit. Statistical analysis was carried out using the STATA statistical package version 13. A p-value of < 0.05was considered to be statistically significant. RESULTS: HIV infected participants had significantly higher mean 25 (OH) D concentration (112 ± 33.4 nmol/L) compared to the HIV uninfected (100 ± 27.1 nmol/L), p = 0.032.Participants whose samples were collected during summer had higher maternal 25 (OH) D levels than those cART duration and maternal 25 (OH) D levels (p = 0.031, Spearman correlation =0.28). CONCLUSIONS: Our findings show high mean levels of maternal 25 (OH) D in late pregnancy in our setting and in the absence of vitamin D supplementation. Both HIV infection and season are significant determinants of maternal vitamin D levels. Summer season is associated with higher maternal plasma 25 (OH) D levels. HIV infection is associated with increased maternal vitamin D levels. Prolonged use of cART, Tenolam E is associated with improved maternal 25(OH) D levels.

Effect of high-dose cholecalciferol (vitamin D3) on bone and body composition in children and young adults with HIV infection: a randomized, double-blind, placebo-controlled trial.

It is unknown whether vitamin D supplementation positively impacts body composition and bone outcomes in children and young adults with HIV. This RCT found that despite increasing 25(OH)D concentrations, high dose vitamin D3 supplementation did not impact bone or body composition in children and young adults with HIV infection. INTRODUCTION: The objective of this paper was to determine the impact of high-dose daily cholecalciferol (vitamin D3) supplementation on body composition and bone density, structure, and strength in children and young adults with perinatally acquired (PHIV) or behaviorally acquired (BHIV) HIV infection. METHODS: Participants were randomized to receive vitamin D3 supplementation (7000 IU/day) or placebo for 12 months. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, dual energy X-ray absorptiometry (DXA) of the whole body and lumbar spine, and peripheral quantitative computed tomography (pQCT) of tibia sites were acquired at 0, 6, and 12 months. DXA and pQCT outcomes were expressed as sex- and population-ancestry specific Z-scores relative to age and adjusted for height or tibia length, as appropriate. RESULTS: Fifty-eight participants (5.0 to 24.9 years) received vitamin D3 supplements (n = 30) or placebo (n = 28). At enrollment, groups were similar in age, sex, population ancestry, growth status, serum 25(OH)D concentrations, body composition, and size-adjusted bone measures. Median 25(OH)D concentrations were similar (17.3 ng/mL in the vitamin D3 supplementation group vs 15.6 ng/mL in the placebo group), and both groups had mild bone deficits. At 12 months, 25(OH)D rose significantly in the vitamin D supplementation group but not in the placebo group (26.4 vs 14.8 ng/mL, respectively, p < 0.008). After adjusting for population ancestry, sex, antiretroviral therapy use, and season, there were no significant treatment group differences in bone or body composition outcomes. CONCLUSIONS: Despite increasing 25(OH)D concentrations, 12 months of high-dose vitamin D3 supplementation did not impact bone or body composition in children and young adults with HIV infection.

Vitamin D status in perinatally HIV-infected Thai children receiving antiretroviral therapy.

BACKGROUND: Low vitamin D level is associated with adverse health outcomes and compromises HIV treatment response. We assess vitamin D status in HIV-infected Thai children receiving combination antiretroviral therapy (cART). METHODS: A cross-sectional study in perinatally HIV-infected children. Vitamin D deficiency and vitamin D insufficiency were defined as serum 25-hydroxyvitamin D (25-OHD) level <20, and 21-29 ng/mL, respectively. RESULTS: Eighty participants were enrolled. Their median age was 12.2 years. The median CD4 lymphocyte count was 784 cell/mm3; 95% had HIV RNA <50 copies/mL. The median (interquartile range, IQR) 25-OHD level was 33.5 (26.2-39.8) ng/mL. Thirty-four (43%) participants had low vitamin D level; 26 (33%) and 8 (10%) had vitamin D insufficiency and deficiency, respectively. In multivariate analysis, only geographic location was significantly associated with low vitamin D level. CONCLUSIONS: Most of perinatally HIV-infected children receiving cART had low vitamin D level. Calcium and vitamin D supplement might be beneficial.

Micronutrient deficiency and treatment adherence in a randomized controlled trial of micronutrient supplementation in ART-naïve persons with HIV.

INTRODUCTION: The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection. OBJECTIVE: We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions. METHODS: Participants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS). RESULTS: Prior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%<1 nmol/L), vitamin D (24%<40 nmol/L) and serum folate (20%<15 nmol/L). The proportion with B12 deficiency (<133 pmol/L) was 2.4%. Lower baseline levels of B12 correlated lower baseline CD4 count (r = 0.21, p = 0.02) with a 21 pmol/L reduction in B12 per 100 cells/µL CD4. Vitamin D levels were higher in men (p<0.001). After a median follow-up of 1.63 years, there were 19 (15%) early withdrawals from the study treatment. Mean treatment adherence using pill count was 88%. Subjective adherence by the GTS was 81% and was moderately but significantly correlated with pill count (r = 0.29, p<0.001). Adherence based on short-term recall (HATS) was >80% in 75% of participants. CONCLUSION: Micronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00798772.