Further evidence to support a recommendation for exclusive breastfeeding by HIV-positive mothers in resource-limited settings was published today by South African researchers in The Lancet. They say it is time to revise UNICEF and World Health Organization (WHO) guidelines on infant feeding in order to promote exclusive breastfeeding more aggressively.
Although exclusive breastfeeding is already recommended by UNICEF and WHO where formula feeding is not available, feasible, affordable, safe and sustainable, the new findings from the Africa Centre for Health and Population Studies define much more clearly the risk of mother to child transmission through breastfeeding during the first months of life, and also demonstrate the differences in transmission risk between women with advanced HIV disease and those with relatively intact immune systems.
They also highlight the degree of risk attached to mixed feeding during the early months of life, especially the introduction of solid food alongside breast milk.
The mucous membrane within the intestine is thought to act as an effective barrier to HIV infection. Breast milk ordinarily strengthens and protects this lining. Exclusive breastfeeding is also associated with fewer breast health problems such as mastitis and breast abscesses, both of which can increase the amount of the HIV virus in the mother's breastmilk. It is unclear why adding solids may be particularly hazardous, though previous research has suggested that the larger, more complex proteins found in solid foods may lead to greater damage to the lining of the stomach, allowing the virus to pass through the gut wall.
The study
Some findings from this study were previously presented at the Sixteenth International AIDS Conference last year in Toronto, and operational aspects of the study were discussed extensively in a special issue of HIV & AIDS Treatment in Practice last September.
The study recruited 1372 HIV-positive pregnant women and 1345 HIV-negative pregnant women in KwaZulu-Natal, South Africa, and assessed feeding practices and the HIV status of their infants during six months follow-up after delivery. It was funded by the Wellcome Trust.
Eighty-two per cent of HIV-positive mothers started exclusive breastfeeding, 7.9% replacement feeding and 2.5% started feeding with a mixture of breastfeeding and other fluids. All women were counselled on infant feeding in their homes three or four times during the first two weeks after delivery, and every two weeks subsequently until the infant was six months old. Mothers kept diaries on infant feeding and health. Complete feeding data for the first six months of life were available for 1276 infants.
Exclusive breastfeeding was defined as breastfeeding only, but mothers were counted in this group if they had engaged in mixed feeding with liquids for a total of less than four separate or continuous days during the study. Giving porridge or any solid food on any occasion was counted as mixed feeding. Replacement feeding was defined as feeding that excluded breast milk entirely, but could include mixed feeding, while mixed breastfeeding was defined as breastfeeding while giving other liquids or solid foods.
HIV testing using a viral load test was carried out on infants at four to eight weeks of age and again at 20-26 weeks of age. Fifteen per cent were infected at four to eight weeks (n=998) (presumably infected during pregnancy or delivery) and 21.6% at week 20-26 (n=962).
Among those infants exclusively breastfed who were HIV PCR-negative at week 6, the transmission rate through breastfeeding during the first six months of life was estimated at 4.04% (confidence interval 2.29 – 5.76%).
However when the transmission rate according to the mode of feeding was analysed, the risk of HIV transmission to infants who were initially breastfed but subsequently began to receive solids alongside breast milk (n=203) was nearly eleven times higher than among infants who were exclusively breastfed (hazard ratio 10.87, CI 1.51 – 78.0, p=0.018).
Infants who received both breast and formula milk at week 14 were twice as likely to become infected as infants given breast milk alone (HR 1.82, CI 1.07 – 3.06, p=0.057). In comparison infants who received only fluids in addition to breast milk were not at significantly greater risk of becoming infected with HIV by month 6 (HR 1.56, p=0.308).
Infants who were exclusively breastfed were significantly less likely to die by month 6 than those that received replacement feeding (6.1% vs 15.1%, HR 2.06, CI 1.00 – 4.27, p=0.051).
Multivariate analysis showed that the risk of transmission to exclusively breastfed infants was strongly influenced by the mother’s immune status, likely representing a surrogate for virus levels in breast milk. Compared with infants born to mothers with a CD4 count above 500 cells/mm3, infants born to mothers with a CD4 cell count between 200 and 500 were 2.2 times more likely to acquire HIV or die (CI 1.63-3.18, p
Low birth weight (12 hours duration after rupture of membranes) and caesarean section were also associated with decreased HIV-free survival.
Lessons from the KwaZulu-Natal study
The study shows, in contrast to large studies in South Africa and Zimbabwe, that with intensive community-based support it is possible for the vast majority of women to sustain exclusive breastfeeding for six months, even using a very stringent definition, say the authors.
The study also confirms that exclusive breastfeeding during the first six months of life carries much less risk of HIV transmission than mixed feeding.
However, the findings follow extensive discussion of infant feeding advice at last month’s Fourteenth Conference on Retroviruses and Opportunistic Infections, where four major studies showed that early weaning at four to six months does not improve HIV-free survival among infants.
Future guidelines on infant feeding will need to balance the well-established finding of an accumulating risk of HIV transmission with greater duration of breastfeeding against the mortality risk of weaning a child too early, a conflict which this study cannot shed light on.
The need to target antiretroviral therapy to eligible breastfeeding mothers
The authors highlight the need for aggressive efforts to identify women with lower CD4 counts to offer them immediate antiretroviral treatment for their own health and that of their child.
“Where such programmes exist, the referral and counselling of pregnant women and initiation of treatment should be an overriding priority and one that should be closely monitored as an indicator of overall programme effectiveness,” they argue.
“The key policy implication of the findings is that we provide definitive data showing that early introduction of solid foods and animal milks increases HIV transmission risks compared to exclusive breastfeeding,” they conclude.
“These data together with evidence of being able to successfully support exclusive breastfeeding in HIV-infected women warrant revision of the current UNICEF/WHO/UNAIDS infant feeding guidelines that were last revised in 2000. The need for this review is reinforced by the reported limitations of free formula milk and recent WHO recommendations for the provision of HAART to pregnant women with CD4 counts lower than 200 cells/mm3."
Coovadia H et al. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding: the first six months of life. The Lancet, March 31 2007.