Interventions for preventing late postnatal mother-to-child transmission of HIV

 

Abstract

Background

Worldwide, mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV) represents the most common means by which children acquire HIV infection.  Efficacious and effective interventions to prevent in utero and intrapartum transmission of HIV infection have been developed and implemented.  However, a large proportion of MTCT of HIV occurs postnatally, through breast milk transmission. 

Objectives

The objectives of this systematic review were to collate and assess the evidence regarding interventions to decrease late postnatal MTCT of HIV, and to determine the efficacy of such interventions in decreasing late postnatal MTCT of HIV, increasing overall survival, and increasing HIV-free survival. 

Search methods

Electronic searches were undertaken using PubMed, EMBASE and other databases for 1980-2008.  Hand searches of reference lists of pertinent reviews and studies, as well as abstracts from relevant conferences, were also conducted.  Experts in the field were contacted to locate any other studies.  The search strategy was iterative.    

Selection criteria

Randomized clinical trials assessing the efficacy of interventions to prevent MTCT of HIV through breast milk were included in the analysis.  Other trials and intervention cohort studies with relevant data also were included, but only when randomization was not feasible due to the nature of the intervention (i.e., infant feeding modality). 

Data collection and analysis

Data regarding HIV infection status and vital status of infants born to HIV-infected women, according to intervention, were extracted from the reports of the studies.

Main results

Six randomized clinical trials and one intervention cohort study were included in this review.  Two trials addressed the issue of shortening the duration of (or eliminating) exposure to breast milk. In a trial of breastfeeding versus formula feeding, formula feeding was efficacious in preventing MTCT of HIV (the cumulative probability of HIV infection at 24 months was 36.7% in the breastfeeding arm and 20.5% in the formula arm [p = 0.001]), but the mortality and malnutrition rates during the first two years of life were similar in the two groups.  In a trial of early cessation of breastfeeding, HIV-free survival was similar between those children who ceased breastfeeding abruptly around four months of age and those who continued breastfeeding.  Another trial addressing vitamin supplementation found more cases of HIV infection among children of mothers in the vitamin A arm.  Efficacy for other vitamin supplements was not shown.  An intervention cohort study evaluated the risk of MTCT by six months of age according to infant feeding modality, and found increased risks of MTCT among breastfed children who also received solids any time after birth (hazard ratio = 10.87, 1.51-78.00, p = 0.018). Cumulative 3-month mortality among formula fed infants was higher than among exclusively breastfed infants (hazard ratio = 2.06, 1.00-4.27, p = 0.051). Three trials evaluated antiretroviral prophylaxis to breastfeeding infants. In one trial conducted in Botswana, mothers received zidovudine prophylaxis beginning at 34 weeks gestation and during labor, and mother and infants were randomized to receive a two-dose nevirapine regimen or placebo.  Infants were randomized to six months of breastfeeding with zidovudine prophylaxis (breastfeeding+zidovudine) or formula feeding with one month of infant zidovudine (formula+zidovudine). Mothers were instructed to initiate and complete weaning between five and six months of age. Breastfeeding+zidovudine (transmission rate = 9.0%) was not as effective as formula+zidovudine (transmission rate 5.6%) in preventing late postnatal HIV transmission (p = 0.04).  Breastfeeding+zidovudine and formula+zidovudine had comparable HIV-free survival rates at 18 months (p = 0.60). Two trials of extended infant nevirapine prophylaxis demonstrated efficacy.  In the first (data combined from trials conducted in three different countries), a six-week course of nevirapine resulted in a lower risk of HIV transmission by six weeks of age (p=0.009), but not at six months of age (p = 0.016).  In the second, mothers were counseled to breastfeed exclusively for six months and to consider weaning thereafter.  Nevirapine administration until 14 weeks of age (5.2%) or nevirapine with zidovudine until 14 weeks of age (6.4%) resulted in significantly lower risks of MTCT of HIV by 9 months of age than a control regimen of two-dose nevirapine prophylaxis (10.6%) (p < 0.001).  HIV-free survival was significantly better through the age of 9 months in both extended prophylaxis groups, and through the age of 15 months in the extended nevirapine group.  

Authors' conclusions

Complete avoidance of breastfeeding is efficacious in preventing MTCT of HIV, but this intervention has significant associated morbidity (e.g., diarrheal morbidity if formula is prepared without clean water).  If breastfeeding is initiated, two interventions 1). exclusive breastfeeding during the first few months of life;  and 2)  extended antiretroviral prophylaxis to the infant (nevirapine alone, or nevirapine with zidovudine) are efficacious in preventing transmission. 

 

Plain language summary

Transmission of HIV from mother to child through breast milk

Mother-to-child transmission (MTCT) of HIV is the primary way that children become infected with HIV.  Such transmission can take place when the child is still in the mother’s womb, around the time of birth, or through breastfeeding after birth.  Hundreds of thousands of children are infected this way every year, with most of them in developing countries.  Major progress has been made in preventing MTCT when the baby is still in the mother’s womb, or around the time the baby is born.  In many resource-rich settings, mothers with HIV infection are counseled not to breastfeed their children, and there are feasible and affordable alternatives to breastfeeding.  However, in parts of the world where the vast majority of mothers with HIV infection live, complete avoidance of breastfeeding is often not feasible (for example, because of the lack of availability of clean water and of affordable replacement feeding).  Therefore, interventions to prevent transmission of HIV infection through breast milk are urgently needed.  The authors found that, in addition to complete avoidance of breastfeeding if safe and affordable, exclusive breastfeeding (where the baby receives only breast milk) for the first few months of life helps prevent transmission (as compared to breastfeeding supplemented by feeding the baby other liquids or solids).  Another intervention, giving the baby an anti-HIV medicine (antiretroviral) while breastfeeding, decreases the risk of transmission of HIV from mother to child. Implementation of such interventions, as well as developing more and better interventions, is essential.

 

摘要

背景

預防後期產後垂直感染後天免疫病毒(HIV)之介入方法

以全世界來講，垂直感染(mothertochild transmission, MTCT)人類後天免疫缺乏病毒(human immunodeficiency virus type 1)是使兒童獲得愛滋病毒感染最常見的原因。有效預防子宮內和產程中傳播愛滋病毒感染的相關介入措施已經被制定並實施。然而，其中有很大比例的母嬰垂直感染是透過產後的母乳傳染。

目標

這篇系統回顧性文章的宗旨，將校對和評估關於減少後期產後母嬰傳染愛滋病毒介入措施之證據，並確定這種介入措施的效果可降低晚期產後母嬰傳播愛滋病毒的機會，提高整體存活率(overall survivial)，並增加無愛滋病毒感染的存活率(HIVfree survival)。

搜尋策略

電子資料搜索包含了使用1980年至2008年期間之PubMed，EMBASE以及和其他電子資料庫。書面資料搜尋則包含了可參考之文獻回顧和研究，以及相關的會議摘要。本研究與該領域的專家進行聯繫，以尋找任何其他相關的研究。本研究的文獻蒐集策略是反覆搜尋(iterative)。

選擇標準

本研究分析中，包括了評估預防兒童藉由餵哺母乳而經母體感染愛滋病毒之介入措施效能的隨機臨床試驗。其他試驗和介入方法的世代研究(intervention cohort studies)也有包含在內，但唯有在當該介入措施無法進行隨機化分配之時(例如：嬰兒餵養方式)。

資料收集與分析

根據介入方法，從研究數據中提取出患有愛滋病的母親所生之嬰兒其愛滋病感染狀態及生命狀態的資料。

主要結論

這篇回顧性研究中包含了六個隨機臨床試驗(randomized clinical trials)以及一個介入方法的世代研究(intervention cohort study)。其中兩個臨床試驗論及了縮短(或停止)餵哺母乳的時間以減少暴露機會。在其中一個比較餵哺母乳和配方乳的臨床試驗中，使用配方乳在預防母嬰傳染愛滋病毒方面是有效果的(在出生24個月內累積感染愛滋病毒的機率方面，餵哺母乳組是36.7%，餵哺配方乳組是20.5%[p = 0.001])，不過在出生後頭兩年的死亡率和營養不良的比率上，兩組的結果是相似的。在一個早期停止餵哺母乳的臨床試驗中，在四個月大時停止餵母乳的小孩與持續餵哺母乳的小孩比較，兩者間無愛滋病毒感染的存活率(HIVfree survival)是相似的。另一個試驗論及在補充維生素的比較中，補充維生素A組發現較多受到母嬰傳染愛滋病毒的案例，而其他維生素的補充則未見其效力。一個介入方法的世代研究中評估不同餵哺方法所造成母嬰傳染病毒的風險，發現同時接受餵哺母乳和固態食物的小孩，相較於非母乳餵哺的小孩，其受到母嬰傳染病毒的風險(hazard ratio = 10.87, p = 0.018)和出生後三月內的死亡率(hazard ratio = 2.06)都較高。有三個試驗評估餵哺母乳的嬰孩上預防性使用抗反轉錄病毒藥物的效果：其中一個試驗發現使用zidovudine來進行預防的餵哺母乳者(傳染率 9.0%)，在預防後期產後愛滋病毒的傳染方面，並不會比餵哺配方乳(傳染率 5.6%)要來的有效(p = 0.04)。餵哺母乳並使用zidovudine預防者，與餵哺配方乳兩者之間，在出生後18個月時具有相近(comparable)的無愛滋病毒感染存活率(p = 0.60)。在兩個臨床試驗中，廣泛性使用nevirapine藥物來預防感染顯示出其效果：其中第一個試驗(資料收集自三個不同國家的臨床試驗)，六週的nevirapine療程可使嬰兒在六週大時有較低的愛滋病毒傳染風險(p = 0.009)，但在六個月大時則無此效果(p = 0.016)。在第二個試驗中，相較於控制組在產程中的預防性藥物使用(peripartum prophylaxis)(10.6%, p < 0.001)，使用nevirapine直到十四週的年齡時(5.2%)，或者同時使用nevirapine和zidovudine直到十四週大時(6.4%)，可顯著的降低在九個月大時母嬰垂直傳染愛滋病毒的風險。 兩個廣泛性藥物預防組在嬰兒九個月大時的無愛滋病毒感染存活率都較佳，而十五個月大時則是廣泛使用nevirapine組的無愛滋病毒感染存活率較佳。

作者結論

徹底避免餵哺母乳是預防母嬰垂直傳染愛滋病毒的有效方法，不過這項介入方法可能造成顯著伴隨而生的問題(例如：使用不乾淨的水源沖泡配方乳可能造成腹瀉的問題)。如果已經開始餵哺母乳，有兩項介入方法可以有效預防傳染：(1)只在嬰兒出生後的前幾個月餵哺母乳, (2) 在嬰兒身上長時間預防性使用抗反轉錄藥物(單用nevirapine，或同時使用nevirapine和zidovudine)。

翻譯人

本摘要由臺北榮民總醫院徐千彝翻譯。

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

總結

經由餵哺母乳造成母嬰垂直傳染愛滋病毒：母對子垂直傳染(Mothertochild transmission, MTCT)是小孩罹患愛滋病毒最主要的原因。這種傳染方式，可以發生在孩子還在母親的子宮，在出生時，或出生後經過餵哺母乳而造成。數以萬計的兒童每年透過這種方式被感染，其中大多數人在發展中國家。預防小孩在母親子宮內或在出生時受到母嬰垂直感染的方法已有了重大進展。在許多資源豐富的情況下，感染愛滋病毒的母親被勸告不要用母乳餵哺自己的孩子，並有可行和負擔得起的替代方法取代母乳餵養。然而，在世界各地絕大多數感染愛滋病毒之母親的生活中，完全避免母乳餵哺往往是不可行的(例如，缺乏清潔的飲水的和負擔得起的替代餵哺方法)。因此，預防經由餵哺母乳而傳染愛滋病毒的介入方法是被迫切需要的。本文的作者發現，除了在安全和負擔得起的前提下完全避免餵哺母乳這個方法之外，只在出生後的前幾個月餵哺母乳(嬰兒只吃母乳)有助於防止傳染(相較於餵哺母乳外還餵養其他的液體或固體食物)。另外一項介入方法，也就是在餵哺母乳時同時給予嬰兒抗愛滋病藥物(抗反轉錄病毒藥物)可以降低母嬰垂直傳染的風險。執行以上這些預防措施，以及開發更多更好的介入方法，是勢在必行的。