Duration, Pattern of Breastfeeding and Postnatal Transmission of HIV: Pooled Analysis of Individual Data from West and South African Cohorts

BackgroundBoth breastfeeding pattern and duration are associated with postnatal HIV acquisition; their relative contribution has not been reliably quantified. Methodology and Principal FindingsPooled data from 2 cohorts: in urban West Africa where breastfeeding cessation at 4 months was recommended but exclusive breastfeeding was rare (Ditrame Plus, DP); in rural South Africa where high rates of exclusive breastfeeding were achieved, but with longer duration (Vertical Transmission Study, VTS). 18-months HIV postnatal transmission (PT) was estimated by Kaplan-Meier in infants who were HIV negative, and assumed uninfected, at age >1 month. Censoring with (to assess impact of mode of breastfeeding) and without (to assess effect of breastfeeding duration) breastfeeding cessation considered as a competing event. Of 1195 breastfed infants, not HIV-infected perinatally, 38% DP and 83% VTS children were still breastfed at age 6 months. By age 3 months, 66% of VTS children were exclusively breastfed since birth and 55% of DP infants predominantly breastfed (breastmilk+water-based drinks). 18-month PT risk (95%CI) in VTS was double that in DP: 9% (7–11) and 5% (3–8), respectively (p = 0.03). However, once duration of breastfeeding was allowed for in a competing risk analysis assuming that all children would have been breastfed for 18-month, the estimated PT risk was 16% (8–28) in DP and 14% (10–18) in VTS (p = 0.32). 18-months PT risk was 3.9% (2.3–6.5) among infants breastfed for less than 6 months, and 8.7% (6.8–11.0) among children breastfed for more than 6 months; crude hazard ratio (HR): 2.1 (1.2–3.7), p = 0.02; adjusted HR 1.8 (0.9–3.4), p = 0.06. In individual analyses of PT rates for specific breastfeeding durations, risks among children exclusively breastfed were very similar to those in children predominantly breastfed for the same period. Children exposed to solid foods during the first 2 months of life were 2.9 (1.1–8.0) times more likely to be infected postnatally than children never exposed to solids this early (adjusted competing risk analysis, p = 0.04). ConclusionsBreastfeeding duration is a major determinant of postnatal HIV transmission. The PT risk did not differ between exclusively and predominantly breastfed children; the negative effect of mixed breastfeeding with solids on PT were confirmed.研究背景：母乳喂养模式与喂养时长均与产后HIV感染相关，但二者的相对贡献尚未得到可靠量化。 方法学与主要研究结果：本研究合并了两个队列的数据：其一为西非城市地区队列（Ditrame Plus, DP），当地建议婴儿4个月时停止母乳喂养，但纯母乳喂养比例极低；其二为南非农村地区队列（Vertical Transmission Study, VTS，垂直传播研究），该队列实现了较高的纯母乳喂养率，但喂养时长更长。针对出生1个月以上HIV检测阴性且假定未感染的婴儿，采用Kaplan-Meier法估算其18个月产后HIV传播（postnatal transmission, PT）风险。以停止母乳喂养作为竞争风险事件，分别开展带删失（用以评估母乳喂养模式的影响）与不带删失（用以评估母乳喂养时长的效应）的分析。本研究共纳入1195名经母乳喂养且未发生围产期HIV感染的婴儿，其中6月龄时仍接受母乳喂养的儿童占比在DP队列中为38%，在VTS队列中为83%。至3月龄时，VTS队列中有66%的儿童自出生起即接受纯母乳喂养，DP队列中有55%的婴儿以母乳喂养为主（母乳+水基饮品）。VTS队列的18个月产后传播风险为9%（95%置信区间, 95%CI：7~11），是DP队列的2倍（DP队列风险为5%，95%CI：3~8），组间差异具有统计学意义（p=0.03）。然而，在考虑母乳喂养时长的竞争风险分析中（假定所有儿童均接受18个月母乳喂养），DP队列的估算产后传播风险为16%（95%CI：8~28），VTS队列则为14%（95%CI：10~18），组间差异无统计学意义（p=0.32）。母乳喂养时长不足6个月的婴儿，其18个月产后传播风险为3.9%（95%CI：2.3~6.5）；母乳喂养时长超过6个月的儿童则为8.7%（95%CI：6.8~11.0）。粗风险比（hazard ratio, HR）为2.1（95%CI：1.2~3.7，p=0.02）；校正后HR为1.8（95%CI：0.9~3.4，p=0.06）。针对特定母乳喂养时长的产后传播率单独分析显示，相同喂养时长下，纯母乳喂养儿童的感染风险与以母乳为主的混合喂养儿童极为相似。出生后前2个月即接触固体食物的儿童，其产后感染HIV的风险是未在该时期接触固体食物儿童的2.9倍（95%CI：1.1~8.0，校正竞争风险分析p=0.04）。 研究结论：母乳喂养时长是产后HIV传播的主要决定因素。纯母乳喂养与以母乳为主的混合喂养儿童的产后传播风险并无差异；添加固体食物的混合喂养方式对产后HIV传播的负面影响得到了证实。