We presented first in an early report  and then in full  our findings that mother-to-child HIV transmission is substantially less among those breast-feeding mothers who maintain exclusive breast-feeding until the child is 3 months of age or older than that among other breast-feeding mothers. The transmission rate observed among exclusively breast-feeding mothers is similar to that observed among mothers who do not breast-feed at all. Our findings opened a new avenue for research, which is important because the avoidance of all breast-feeding is not a realistic option for most HIV-infected women in southern Africa. Failure to breast-feed substantially increases morbidity and mortality rates from other diseases in early childhood . In many circumstances, breast milk substitutes are unavailable, are prohibitively expensive, or cannot be prepared hygienically. In many societies, breast-feeding is culturally entrenched and deeply valued, and failure to breast-feed may be a tacit disclosure of HIV status in situations in which breast-feeding is near universal. The importance of breast-feeding for maternal and child health in developing countries demands of us the cautious and critical appraisal of any practices that may undermine it. We thus appreciate the serious attention that has been given to our findings by Forsyth  and Walker et al. .
The first concern raised by Forsyth  about the ‘remarkably low’ rate of transmission over the first few weeks of life in the exclusive breast-feeding group is, however, based on a misunderstanding of the presentation of our results. The first protocol-scheduled HIV test in the child after the first week test was at 6 weeks. At 6 weeks, the rate of transmission in the exclusive breast-feeding group (15%) was remarkably similar to that observed in the never breast-fed group (18%). Given our method of analysis, it is not possible to make good inferences about the transmission rates in the time periods when testing was not scheduled to take place.
The second concern raised by Forsyth , which might be described as a ‘healthy survivor bias’ warrants careful analysis. We investigated whether or not child morbidity preceded shifting away from exclusive breast-feeding to mixed breast-feeding. It did not. We investigated whether or not markers of the severity of maternal HIV disease were associated with the ability to maintain exclusive breast-feeding to 3 months. They were not. We investigated whether or not intrauterine transmission rates were different in the groups. They were not. In sum, we did not observe associations consistent with this hypothesized bias. To investigate further a possible ‘survivor bias', we would like to present the results on only those children who survived to 3 months of age, thus excluding those children hypothesized to bias the results (Fig. 1). Consistent with the other data we have already presented, transmission rates in this sub-group of children surviving to 3 months were highest in mixed breast-fed infants, and similar between exclusively breast-fed and never breast-fed infants up until approximately the age at which no more exclusive breast-feeding continued.
In our paper we presented two complementary analyses. The first was based on Kaplan–Meier curves with a fixed covariate for feeding practice and the second was based on a Cox proportional hazards model with a time-dependent covariate for feeding practice. Contrary to the assertion by Walker et al. , this second analysis (which they consider the ‘correct’ one) generated almost exactly the same findings as the first analysis (which they consider the ‘inappropriate’ one). Exclusive breast-feeding was associated with almost half the instantaneous risk of HIV transmission (hazard ratio 0.56, 95% confidence interval 0.32–0.98) compared with mixed breast-feeding. The magnitude of this hazard ratio was unchanged after adjusting for many covariates. Only considerably larger studies would be able to separate out age-specific risks.
Our findings raise many questions in need of further research beyond the simple repetition of the main findings. These include investigation of how to support exclusive breast-feeding among HIV-infected women who elect to breast-feed. Exclusive breast-feeding is very rare in most parts of Africa, even in those regions where breast-feeding is almost universal and of long duration. For instance, DHS surveys estimate the prevalence of exclusive breast-feeding among children of 2–4 months of age to be 27% in Zambia, 17% in Kenya, and 11% in Malawi . We need to obtain a better understanding of the relationships between exclusive breast-feeding and breast pathology, including sub-clinical mastitis; factors that appear to play an important role in post-natal HIV transmission [7,8]. We need to evaluate better options for mothers and babies after 6 months of age when breast-feeding can no longer be exclusive. A polarized argument in support of breast-feeding or in support of formula feeding offers little in the way of scientific insight into how best to minimize the risks of post-natal HIV transmission through breast-feeding, without creating new problems for maternal and child health.
Hoosen M. Coovadiaa
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