HIV+ mothers without ART: when and how should they wean?

Without antiretrovirals, breastfeeding contributes 28% to the risk of mother-to-child HIV transmission (MTCT) (http://sti.bmj.com/content/88/Suppl_2/i44.abstract?sid=fcfaeecc-767f-4db8-b644-77db5aa8db63).  Antiretroviral drugs make achieving he WHO goal of near elimination of MTCT imaginable (http://sti.bmj.com/content/87/3/261.full; http://sti.bmj.com/content/86/Suppl_2/ii48.abstract?sid=fcfaeecc-767f-4db8-b644-77db5aa8db63).  But, in the meantime, what advice should be given to HIV+ mothers in those low-resource settings where antiretrovirals are still not available?

In this context, the health benefits of breastfeeding may yet override the risks of MTCT, as indicated by recent WHO guidance (http://depts.washington.edu/ghivaids/reslimited/case5/discussion.html#ref).  But when and how should infants be weaned in order to minimize the inevitable risk?  To give the best advice, we need to know more about how MTCT takes place.  A recent study (Louise Kuhn et al.) seeks to fill gaps in our knowledge by examining the relation between weaning and HIV concentration in breast milk (http://stm.sciencemag.org/content/5/181/181ra51.abstract?sid=c20e20f7-1f36-474d-99dc-ac2c265d505f).

958 Zambian mothers and their infants were randomized to wean abruptly (4 months) or continue breastfeeding, and HIV concentrations were measured at 4 and 4.5 months.  Two weeks after weaning HIV-1 concentrations in the milk of the abrupt weaners – median RNA, 2780 copies/ml. ; DNA, 14 copies/ml. – were observed to be dramatically higher than for non-abrupt weaners – median RNA, <50 copies/ml.;  DNA, <1 copy/ml..  Furthermore, HIV concentrations were higher even where breast-feeding was non-exclusive (median RNA 293 copies/ml.; DNA, 2 copies/ml.).

It would appear from this that the risks of MTCT are not evenly distributed over the period during which the child is breastfed, but spike quite abruptly at the time when weaning takes place.  The physiological explanation of this phenomenon remains unclear; the authors propose as most likely the opening of the paracellular tight junctions of the mammary gland, which is known to occur during weaning.  The fact that other studies have reported no association between non-exclusive breast-feeding and HIV-1 concentrations may, in the authors’ view, be attributable to their failure to focus on the short interval of time following disruption of full breast-feeding.

The validity of these findings, if confirmed by further studies, lends weight to the existing WHO recommendation for mothers to reduce breast-feeding frequency gradually over the weeks leading up to the last planned breast milk feed (http://www.avert.org/pmtct-guidelines.htm).  Evidently, abrupt weaning following exclusive breast-feeding, if genuinely achieved, would eliminate the PMCT risk through breast milk (though weaning abruptly is associated with maternal morbidity).  The problem, however, is that even minimal deviation from abrupt weaning presents the most acute risk of PMTC.

So, gradual weaning seems advisable, accompanied, as the authors suggest, by the expression and discarding of breast milk to relieve engorgement.  Where antiretrovirals are being offered for the child’s health, HIV-1 infected women should continue the antiretrovirals they used through lactation over the full duration of time when any breast milk exposures occur.  Existing WHO guidelines regarding ART regimes for these mothers stipulate that drugs should be continued until one week after breastfeeding is finished (http://www.avert.org/pmtct-guidelines.htm).  The authors point out that in the light of their findings, the “one or two-week period” that “has been considered adequate” may be too short.  At all events the existing WHO guidelines seem inadequate, given the complexity of the practical issues surrounding weaning, and the acuteness of PMTC risk concentrated at this stage.

This study focuses on the issue of weaning as it presents itself for breast-feeding mothers without ART.  The authors point to the urgent need for further research of the dynamics of PMCT through breast-milk when ART is being given.  They also urge the importance of pursuing the same investigation in relation to the weaning of the older infant – given the WHO guidelines have now shifted to encourage weaning at a later stage (post 12 months).  Further clarification through research in this area seems urgently needed.

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