Vitamin D₃ Supplementation in Batswana Children and Adults with HIV: A Pilot Double Blind Randomized Controlled Trial

Steenhoff, Andrew P.; Schall, Joan I.; Samuel, Julia L.; Seme, Boitshepo; Marape, Marape; Ratshaa, Bakgaki; Goercke, Irene; Tolle, Michael A.; Nnyepi, Maria; Mazhani, Loeto; Zemel, Babette S.; Rutstein, Richard M.; Stallings, Virginia A.

doi:10.1371/journal.pone.0117123

Cited by 30 publications

(42 citation statements)

References 26 publications

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“…According to a recent review by Mansueto et al [ 96 ] the prevalence of vitamin D deficiency among HIV-infected individuals in both RLS and RRS varies widely across studies ranging from 25 to 93%, with an overall prevalence of 70.3 to 83.7%. Similarly, our review yielded high but similar prevalence of low vitamin D among HIV individuals regardless of ART use in both RLS [ 50 , 53 , 97 – 102 ] and RRS [ 61 , 103 – 109 ] with insufficient levels of up to 90% in Turkey [ 50 ] and the USA [ 103 ], Belgium [ 108 ], Spain [ 109 ] (Table 2 and Fig. 2 ).…”

Section: Introductionsupporting

confidence: 54%

Bone health and HIV in resource-limited settings

Matovu

Wattanachanya

Beksinska

et al. 2016

Current Opinion in HIV and AIDS

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Purpose of reviewSub-Saharan Africa and other resource-limited settings (RLS) bear the greatest burden of the HIV epidemic globally. Advantageously, the expanding access to antiretroviral therapy (ART) has resulted in increased survival of HIV individuals in the last 2 decades. Data from resource rich settings provide evidence of increased risk of comorbid conditions such as osteoporosis and fragility fractures among HIV-infected populations. We provide the first review of published and presented data synthesizing the current state of knowledge on bone health and HIV in RLS.Recent findingsWith few exceptions, we found a high prevalence of low bone mineral density (BMD) and hypovitaminosis D among HIV-infected populations in both RLS and resource rich settings. Although most recognized risk factors for bone loss are similar across settings, in certain RLS there is a high prevalence of both non-HIV-specific risk factors and HIV-specific risk factors, including advanced HIV disease and widespread use of ART, including tenofovir disoproxil fumarate, a non-BMD sparing ART. Of great concern, we neither found published data on the effect of tenofovir disoproxil fumarate initiation on BMD, nor any data on incidence and prevalence of fractures among HIV-infected populations in RLS.SummaryTo date, the prevalence and squeal of metabolic bone diseases in RLS are poorly described. This review highlights important gaps in our knowledge about HIV-associated bone health comorbidities in RLS. This creates an urgent need for targeted research that can inform HIV care and management guidelines in RLS.Video abstract:http://links.lww.com/COHA/A9.

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Section: Introductionsupporting

confidence: 54%

Bone health and HIV in resource-limited settings

Matovu

Wattanachanya

Beksinska

et al. 2016

Current Opinion in HIV and AIDS

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“…28,29 Moreover, participant characteristics such as age and body mass index have been reported to modify the 25(OH)D response to vitamin D supplementation. 32,33 Administration of large boluses of vitamin D has been associated with reduced efficacy for non-classical effects 20 and, in some cases, increased risk of adverse outcomes. 34 Although study-level factors are amenable to exploration via aggregate data meta-analysis of published data, potential effect modifiers operating at an individual level, such as baseline vitamin D status, can only be explored using individual participant data (IPD) meta-analysis.…”

Section: Chapter 1 Backgroundmentioning

confidence: 99%

Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis

Martineau

Jolliffe

Greenberg

et al. 2019

Health Technol Assess

279

260

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Background Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. Objectives To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. Data sources MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. Study selection Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. Study appraisal Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. Results We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Limitations Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. Conclusions Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. Study registration This study is registered as PROSPERO CRD42014013953. Funding The National Institute for Health Research Health Technology Assessment programme.

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“…Serum 25(OH)D increased slightly in the supplemented patients, and declined in those not given a supplement. Other studies among HIV patients have also shown an increase in serum 25(OH)D with vitamin D supplementation (12,13,32,33) . Longitudinal studies in HIV patients without vitamin D supplementation (34,35) have reported a decrease in serum 25(OH)D with ART initiation as observed in our study.…”

Section: Discussionmentioning

confidence: 87%

Change in serum 25-hydroxyvitamin D with antiretroviral treatment initiation and nutritional intervention in HIV-positive adults

et al. 2016

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Low vitamin D level in HIV-positive persons has been associated with disease progression. We compared the levels of serum 25-hydroxyvitamin D (25(OH)D) in HIV-positive and HIV-negative persons, and investigated the role of nutritional supplementation and antiretroviral treatment (ART) on serum 25(OH)D levels. A randomised nutritional supplementation trial was conducted at Jimma University Specialized Hospital, Ethiopia. The trial compared 200 g/d of lipid-based nutrient supplement (LNS) with no supplementation during the first 3 months of ART. The supplement provided twice the recommended daily allowance of vitamin D (10 μg/200 g). The level of serum 25(OH)D before nutritional intervention and ART initiation was compared with serum 25(OH)D of HIV-negative individuals. A total of 348 HIV-positive and 100 HIV-negative persons were recruited. The median baseline serum 25(OH)D level was higher in HIV-positive than in HIV-negative persons (42·5 v. 35·3 nmol/l, P17 kg/m2 were randomised to either LNS supplementation (n 189) or no supplementation (n 93) during the first 3 months of ART. The supplemented group had a 4·1 (95 % CI 1·7, 6·4) nmol/l increase in serum 25(OH)D, whereas the non-supplemented group had a 10·8 (95 % CI 7·8, 13·9) nmol/l decrease in serum 25(OH)D level after 3 months of ART. Nutritional supplementation that contained vitamin D prevented a reduction in serum 25(OH)D levels in HIV-positive persons initiating ART. Vitamin D replenishment may be needed to prevent reduction in serum 25(OH)D levels during ART.

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Vitamin D₃ Supplementation in Batswana Children and Adults with HIV: A Pilot Double Blind Randomized Controlled Trial

Cited by 30 publications

References 26 publications

Bone health and HIV in resource-limited settings

Bone health and HIV in resource-limited settings

Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis

Change in serum 25-hydroxyvitamin D with antiretroviral treatment initiation and nutritional intervention in HIV-positive adults

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