Efficacy of vitamin D3 supplementation for the prevention of pulmonary tuberculosis and mortality in HIV: a randomised, double-blind, placebo-controlled trial.,The Lancet HIV

当前位置： X-MOL 学术 › Lancet HIV › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Efficacy of vitamin D3 supplementation for the prevention of pulmonary tuberculosis and mortality in HIV: a randomised, double-blind, placebo-controlled trial.
The Lancet HIV ( IF 16.1 ) Pub Date : 2020-07-01 , DOI: 10.1016/s2352-3018(20)30108-9
Christopher R Sudfeld ₁ , Ferdinand Mugusi ₂ , Alfa Muhihi ₃ , Said Aboud ₄ , Tumaini J Nagu ₂ , Nzovu Ulenga ₃ , Biling Hong ₅ , Molin Wang ₆ , Wafaie W Fawzi ₇

Affiliation

Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Management and Development for Health, Dar es Salaam, Tanzania.
Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.

Background

Observational data suggest that low vitamin D status is associated with an increased incidence of pulmonary tuberculosis and mortality among people living with HIV. The primary aims of this study were to assess the effect of vitamin D₃ supplementation on the risk of mortality and incidence of pulmonary tuberculosis among adults initiating antiretroviral therapy (ART).

Methods

This was a randomised, double-blind, placebo-controlled trial of vitamin D₃ supplementation among adults living with HIV who initiated ART and had serum 25-hydroxyvitamin D concentrations of less than 30 ng/mL at four large HIV care and treatment centres in Dar es Salaam, Tanzania. Patients were excluded if they were younger than 18 years, pregnant at the time of randomisation, or were enrolled in any other clinical trial. Patients were randomly assigned 1:1 to receive either weekly oral 50 000 IU vitamin D₃ supplements (cholecalciferol) for the first month of ART followed by daily 2000 IU vitamin D₃ supplements or a matching weekly and daily placebo regimen. The randomisation list was computer-generated by a non-study statistician with sequence blocks of ten that were stratified by study clinic. Complete allocation concealment was ensured and patients, field team, and investigators were masked to group assignment. The trial follow-up duration was 1 year and the primary efficacy outcomes were death and incident pulmonary tuberculosis. An intention-to-treat analysis was followed for all-cause mortality; participants diagnosed with or receiving treatment for pulmonary tuberculosis at randomisation, or suspected to have tuberculosis at randomisation and who later had that diagnosis confirmed, were excluded from analyses of pulmonary tuberculosis incidence. Safety was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT01798680, and is completed.

Findings

Between Feb 24, 2014, and Feb 24, 2017, 6250 adults initiating ART had serum 25-hydroxyvitamin D screening, 4000 of whom were enrolled in the trial and followed up for 1 year (follow-up of all participants was completed on March 7, 2018). 2001 patients were randomly assigned to the vitamin D₃ supplementation group, and 1999 to the placebo group. 415 deaths were recorded: 211 in the vitamin D₃ group and 204 in the placebo group. Among all randomly assigned participants, there was no overall effect of vitamin D₃ supplementation on the risk of mortality (hazard ratio [HR] 1·04, 95% CI 0·85–1·25; p=0·73). There was also no difference in the overall incidence of pulmonary tuberculosis between the vitamin D₃ (50 events in 1812 patients analysed) and placebo groups (64 events in 1827 patients; HR 0·78, 0·54–1·13; p=0·19). The vitamin D₃ regimen did not increase the risk of hypercalcaemia (three events in the vitamin D₃ group and two events in the placebo group; relative risk 1·25, 95% CI 0·43–3·66; Fisher's exact p=1·00). 101 hospital admissions were reported in the vitamin D₃ group and 94 in the placebo group (incidence rate ratio 1·06, 95% CI 0·80–1·41; p=0·66).

Interpretation

Additional research is needed before vitamin D₃ supplementation should be considered for implementation in HIV care and treatment programmes for the prevention of pulmonary tuberculosis or mortality.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases.

中文翻译：

补充维生素D3预防肺结核和HIV死亡的功效：一项随机，双盲，安慰剂对照试验。

背景

观察数据表明，低维生素D状态与艾滋病毒携带者中肺结核的发病率增加和死亡率增加有关。这项研究的主要目的是评估补充维生素D ₃对开始抗逆转录病毒治疗（ART）的成年人的死亡风险和肺结核发生率的影响。

方法

这是一项随机，双盲，安慰剂对照的维生素d试₃补充艾滋病毒感染者的成年人是谁发起艺术之中，并在四个大型艾滋病关怀治疗中心少于30毫微克/毫升的血清25-羟维生素d含量坦桑尼亚达累斯萨拉姆。如果患者未满18岁，在随机分组时已怀孕或参加了其他任何临床试验，则将其排除在外。患者被随机分配为1：1，在ART的第一个月每周接受口服50000 IU维生素D ₃补充剂（胆钙化醇），然后每天接受2000 IU维生素D ₃补充剂或匹配的每周和每日安慰剂治疗方案。随机对照表由一名非研究统计学家通过计算机生成，并由研究诊所进行了分层，每个序列有十个。确保完全隐藏分配，并且掩盖了患者，现场团队和调查人员进行小组分配。试验随访时间为1年，主要疗效结果为死亡和肺结核事件。对所有原因的死亡率进行意向性治疗分析。被随机诊断为肺结核或接受治疗的参与者，或被随机诊断为肺结核且后来被确诊的参与者，被排除在肺结核发病率分析之外。在意向治疗人群中评估安全性。

发现

在2014年2月24日至2017年2月24日之间，有6250名开始接受抗逆转录病毒疗法的成年人进行了血清25-羟基维生素D筛查，其中4000名患者参加了该试验，并进行了为期1年的随访（所有参与者的随访于3月7日完成），2018）。2001年患者被随机分配至维生素D ₃补充剂组，1999年患者被分配至安慰剂组。记录了415例死亡：维生素D ₃组211例和安慰剂组204例。在所有随机分配的参与者中，补充维生素D ₃对死亡风险没有总体影响（危险比[HR] 1·04，95％CI 0·85-1·25； p = 0·73）。维生素D ₃之间的肺结核总发病率也没有差异（已分析1812位患者的50个事件）和安慰剂组（1827位患者的64个事件； HR 0·78、0·54-1·13； p = 0·19）。维生素D ₃方案不会增加高钙血症的风险（维生素D ₃组为_3个事件，安慰剂组为2个事件；相对风险1·25，95％CI 0·43-3·66； Fisher精确p = 1·00）。维生素D ₃组报道了101例入院，安慰剂组报道了94例（发生率比1·06，95％CI 0·80-1·41； p = 0·66）。