Infant-feeding patterns and HIV-1 transmission.

Sir—Anna Coutsoudis and colleagues’ (Aug 7, p 471) findings that mixed breastfeeding accounts for most HIV1 transmission from breastfeeding, and that exclusive breastfeeding may be more protective than formula feeding, are provocative. Although mothers choosing breastfeeding are already advised to breastfeed exclusively, confirmation of their hypothesis would have important implications for safer infant-feeding strategies. However, to evaluate the strength of the evidence, additional information is needed. Their report contains confusing data on timing of infection, and does not provide key information on potential confounders related to choice of feeding method. Coutsoudis and colleagues indicate that 20% of infections among neverbreastfed infants were first detected after age 1 month, but it is not clear whether those infants had been tested at 1 month. Nearly all HIV-1 infections among non-breastfed infants should be detectable by 1 m o n t h , particularly with the more sensitive RNA PCR test (did they use the new Amplicor version 1.5, which is sensitive to non-B subtypes?). The timing of transmission data that they present may reflect missing early collections, suboptimum diagnostic sensitivity, or misclassification (eg, mixed-fed infants classified as f o r m u l a f e d ) . An expanded transmission table showing the number of infants at risk, tested, and found to be infected at different timepoints, is necessary to evaluate the findings, as well as a comment on the consistency of the test results. Would timing of infection be better represented by the midpoint between last negative and first positive test? In addition, because transmission during the first month among infants exclusively breastfed for at least 3 months was surprisingly low (1·9%), infection rates for the additional infants exclusively breastfed for at least 1 month are of interest. Coutsoudis and colleagues’ findings could have been confounded by the reasons for choice of feeding method, viral load, or other factors. The high relative risk associated with mixed feeding (chosen despite counselling promoting exclusive breastfeeding) could have been seen if non-exclusive breastfeeding were related to maternal illness, mastitis, perception of inadequate milk or other feeding problems, or infant illness. If the women who did not choose exclusive breastfeeding had higher viral loads, which is a much stronger risk factor for transmission than CD4-cell to CD8-cell ratio or other factors a s s e s s e d , this fact could also explain differences in transmission between groups. In addition, the study was a vitamin A trial that included a large maternal dose at delivery, so immunoprotection from vitamin A was likely to be higher in breastfed infants. Finally, RNA-positive infants who died before age 3 months were not, it seems, included in the group who were exclusively breastfed for at least 3 months (by definition), but were included in the other two groups. Coutsoudis et al should be congratulated for prompting investigators to rethink how to describe infant feeding. Nevertheless, their interpretation needs to be supported by a more complete presentation of the early transmission data, and careful consideration of how the association between feeding method and HIV transmission risk in this observational study might be confounded by reasons for choice of feeding method, viral load, or other unmeasured factors.