Iron supplementation for reducing morbidity and mortality in children with HIV

 

Abstract

Background

The most prevalent haematologic disturbance associated with HIV in children (apart from CD4 lymphocytopenia) is anaemia. Anaemia associated with HIV arises from multiple mechanisms, including the direct inhibitory effect of HIV on red cell precursors, other locally prevalent and/or opportunistic infections, micronutrient deficiency, anaemia of chronic disease, and as a consequence of medicines given for HIV and/or other concurrent illnesses. Iron deficiency is the most common cause of nutritional anaemia globally. There is significant geographical overlap of areas of the world where iron deficiency anaemia (IDA) and paediatric HIV are distributed. Given the high prevalence of IDA, it is likely that many HIV-infected children also are iron deficient. The contribution of iron deficiency to anaemia in HIV-infected children has been described but is incompletely understood. Currently, iron supplementation for anaemic infants and children is routinely practiced without any obvious effect in most developing countries, which bear most of the burden of global paediatric HIV infections.

Because iron deficiency and IDA are common in HIV-infected children in high-prevalence areas and because there are concerns about possible deleterious effects of iron, this review aims to assess the evidence for iron supplementation for reducing morbidity and mortality in HIV-infected children.

Objectives

To determine whether iron supplementation improves clinical, immunologic, and virologic outcomes in children infected with HIV

Search methods

We used the comprehensive search strategy developed specifically by the Cochrane HIV/AIDS Review Group to identify HIV/AIDS randomised controlled trials, and searched the following electronic databases: MEDLINE (searched November 2007); Embase (searched December 2007); and CENTRAL (December 2007). This search was supplemented with a search of AIDSearch (searched December 2007) and NLM Gateway (searched December 2007) to identify relevant conference abstracts, as well as a search of the reference lists of all eligible articles. The search was not limited by language or publication status.

Selection criteria

Randomised controlled trials (RCTs) of iron supplementation in any form and dose in HIV-infected children aged 12 years and younger.

Data collection and analysis

We independently screened the results of the search to select potentially relevant studies and to retrieve the full articles. We independently applied the inclusion criteria to the potentially relevant studies.
No studies were identified that fulfilled the selection criteria.

Main results

No RCTs of iron supplementation in HIV-infected children were found.

Authors' conclusions

Implications for clinical practice:

The current clinical practice of iron supplementation in HIV-infected children is based on weak evidence comprising observational studies and expert opinions.

Implications for research:

High-quality RCTs of iron supplementation are urgently required, especially in areas with significant overlap of high prevalence of HIV, iron deficiency anaemia, and malaria. Policy makers should prioritise funding for these trials.

 

Plain language summary

Giving iron supplements to improve outcomes in children with HIV/AIDS

Anaemia is one of the most common haematologic problem found in children with HIV/AIDS, second only to depletion of CD4/helper T lymphocytes. Anaemia in HIV-infected children can be caused by direct effects of HIV, other prevalent infections and opportunistic infections on blood producing cells; micronutrient deficiencies; or side effects of drugs used to prevent or treat opportunistic infections and HIV. Deficiency of iron, a micronutrient, is by far the most common cause of nutritional anaemia worldwide. Given the global prevalence of iron deficiency anaemia, especially in parts of the world where childhood HIV infections are quite prevalent, it is likely many HIV-infected children also are iron deficient. There is very little known, however, about the contribution of iron deficiency to anaemia observed in children with HIV/AIDS. Iron supplementation currently is given routinely to anaemic children in most of the developing countries where there also are high rates of HIV infection, and no obvious adverse effects have been observed. However, there are reports of a deleterious effect of iron supplementation during ongoing infections, including malaria. As iron deficiency and iron deficiency anaemia are common in HIV-infected children in high-prevalence areas with concerns about possible deleterious effects of iron, we looked for randomised clinical trials that demonstrated benefits or disadvantages of iron supplements, regardless of type or preparation. We did not find any such trials and conclude that there is a need for large multi-centre trials to examine these questions.

 

摘要

背景

鐵質補充對於患有愛滋病病毒孩童患病率與死亡率的影響

在患有愛滋病病毒孩童身上最常見的血液學異常是貧血(除CD4淋巴球減少外). 患有愛滋病病毒的患者發生貧血可能由許多原因引起,包括愛滋病病毒直接對紅血球前驅細胞的抑制作用,其它像是區域性盛行的或伺機性感染,營養素缺乏,慢性疾病引發之貧血以及治療後天免疫缺乏症候群的藥物或本身同時患有的其它疾病所造成的貧血. 鐵質缺乏是全世界因營養不良導致貧血最常見的原因之一. 缺鐵性貧血與罹患愛滋病病毒孩童的地域性分佈是有明顯的共同性. 因為缺鐵性貧血的盛行率是很高的,所以感染愛滋病病毒的孩童可能同時合併著鐵質缺乏的問題. 鐵質缺乏與感染愛滋病病毒孩童的貧血之間的相關性是有被記載過,但是兩者如何互相影響目前並不清楚. 現今,雖然在已開發國家的紀錄中沒有明顯的效果,對於貧血的嬰兒和孩童,鐵劑補充是被例行性執行的. 而這些嬰兒與孩童大部分是感染愛滋病病毒. 因為在盛行率高的地區罹患愛滋病病毒的孩童發生鐵質缺乏與缺鐵性貧血是很普遍的,且因為鐵劑補充可能帶來不好的副作用,這篇文章評估針對以鐵劑的補充來減少患有愛滋病病毒孩童的患病率及死亡率的證據性.

目標

評估鐵質補充對於患有愛滋病病毒孩童的臨床症狀,免疫功能,病毒感染的改善情況.

搜尋策略

我們的綜合性搜尋策略是利用考科藍針對愛滋病病毒/後天免疫不全症候群的檢閱小組去找出有關於愛滋病病毒/後天免疫不全症候群的隨機控制研究,而搜尋的電子資料庫包含以下所列: MEDLINE (searched November 2007); Embase (searched December 2007); and CENTRAL (December 2007). 我們的搜尋也藉著 AIDSearch (searched December 2007) and NLM Gateway (searched December 2007)來找出相關研討會的結論與參考資料上所列適合的文章. 這些搜尋的內容並不受限於語言或出版狀態.

選擇標準

針對12歲或更年輕染愛滋病病毒的小孩補充不論劑型或劑量的鐵質做隨機控制的研究

資料收集與分析

我們分別地對每一個研究結果做篩檢來選出相關的研究且蒐集全文. 我們訂出適用的規範對可能適用的文章篩選. 但是並沒有文章完全地符合我們的適用規範.

主要結論

現今並沒有針對在感染愛滋病孩童身上補充鐵劑的隨機控制研究.

作者結論

臨床應用的情形: 現今針對在感染愛滋病孩童身上補充鐵劑僅根據ㄧ些由觀察得到結論的研究與專家意見所建立的微弱證據. 研究情形: 高品質的針對在感染愛滋病孩童身上補充鐵劑的隨機控制研究是迫切必須的,尤其在那些愛滋病與缺鐵性貧血與瘧疾盛行率都很高的區域. 政策決定者應優先的提供這方面研究經費.

翻譯人

本摘要由臺北榮民總醫院巫炳峰翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

鐵質補充是否可以改進患有愛滋病病童的預後: 貧血在患有愛滋病病毒的孩童是最常見的血液問題,僅次於缺乏CD4 T淋巴球. 貧血在患有愛滋病病毒的孩童可能的原因是直接由愛滋病病毒引發,或是由其它地區性常見和伺機性感染而影響造血細胞, 營養不良, 治療或預防伺機性感染與愛滋病藥物的副作用所致. 輕微營養不良造成的鐵質缺乏是目前全世界最常見的營養性貧血. 鑑於全球普遍存在的缺鐵性貧血症，尤其是某些地區在孩童時期感染愛滋病病毒的情況非常普遍，很可能許多感染愛滋病毒的兒童也有鐵質缺乏的問題. 然而, 目前對於鐵質缺乏造成罹患愛滋病毒/愛滋病兒童貧血的關係並不十分清楚. 在大多數發展中國家裡, 愛滋病的感染率是很高的, 鐵質補充是例行性地給予貧血的孩童而且並沒有發現什麼不好的副作用. 但是，有報導指出在一些正在罹患感染症的病人身上給予鐵劑的補充是有害的, 其中包括瘧疾. 在高發病率地區, 由於缺鐵和缺鐵性貧血在感染愛滋病毒的兒童上是常見的,同時考慮到鐵劑補充可的副作用, 我們期待不論形式或種類的隨機臨床試驗可以證實鐵劑補充的好處與壞處. 我們沒有找到任何這種研究試驗, 所以需要大型多中心的研究試驗對這個問題做更深入的探討.