HIV: Balancing Maternal & Infant Benefits & the Consequences of Breast-Feeding

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The Journal of Infectious Diseases 2007;195:165-167© 2006 by the Infectious Diseases Society of America. All rights reserved.0022-1899/2007/19502-0002$15.00

EDITORIAL COMMENTARY

Balancing Maternal and Infant Benefits and the Consequences of Breast-Feeding in the Developing World during the Era of HIV Infection

M. Wilfert1,2 and Glenn Fowler3,4

1 Glaser Pediatric AIDS Foundation, Washington, DC; 2Department of Pediatric Infectious Diseases, Duke University Medical Center, Durham, North Carolina; 3Department of Pathology, s Hopkins Medical Institute, Baltimore, land; 4Makerere University, s Hopkins University Research Collaboration, Kampala, Uganda (See the article by Otieno et al., on pages 220–9.) Received 30 May 2006; accepted 21 August 2006; electronically published 13 December 2006. Potential conflicts of interest: none reported. Reprints or correspondence: Dr. M. Wilfert, 1917 Wildcat Creek Rd., Chapel Hill, NC 27516 (wilfert@...).

The issue of breast-feeding among HIV-infected women in resource-limited settings presents major challenges for maternal and infant health and survival. Not only are there concerns about the possible negative effects of prolonged breast-feeding on maternal health, but the need to balance the protective effect of breast-feeding against other competing causes of infant mortality and the low but ongoing risk of infant HIV acquisition via breast milk is a persisting issue.

We currently know how to safely and effectively decrease mother-to-child transmission of HIV, both prenatally and intrapartum. When optimal prenatal and intrapartum interventions are given to the mother and postpartum prophylaxis is provided to the newborn, transmission rates can be reduced to 1%–2% [1–3]. However, in resource-limited settings—where breast-feeding is the norm—postpartum transmission of HIV-1 via breast-feeding continues to be a major unresolved public health dilemma; HIV-1 transmission via breast milk ranges from 8%–16% [4–6] when lactation continues into the second year. In these settings, where it is not possible to adequately nourish an infant with replacement feeding, infant mortality is significantly increased among infants who are not breast-fed [7].

In the context of making decisions about infant feeding, there is a need to better inform health care providers to supply appropriate counseling given the setting and woman's circumstances. For example, it is not well understood by many health care providers and pregnant women that HIV-1 is transmitted only to a subpopulation of infants and that the actual risk for transmission per month after the first 2 months of life is quite low—6–9 infant transmission events per 1000 infants exposed to breast-feeding per month. Recent published findings from a Botswana perinatal trial [8] document a mortality rate at 7 months of age in formula-fed infants that is almost twice as high as that in breast-fed infants. After weaning in the breast-fed group, HIV-free survival was comparable by 18 months of age. One must conclude that, although replacement feeding did reduce HIV transmission to infants, it was at the cost of creating substantial additional risks for other-cause mortality and did not reduce overall infant mortality. Unpublished data from Botswana have further documented a large and serious outbreak of diarrhea with attendant malnutrition and death in children <2 years of age who were receiving replacement feeding [9].

Shortening the duration of breast-feeding will diminish exposure to the risk of HIV infection, which is ongoing and cumulative. However, this is countered by increased risks of malnutrition and competing causes of infant mortality in resource-limited settings, where breast milk contributes substantively to the energy requirements of infants into the second year of life. It has been estimated that approximately half of the energy requirements of 6–8-month-old infants, 44% of the requirements of 9–11-month-old infants, and a third of the requirements of 12–23-month-old infants is supplied by breast milk [10]. If an infant is weaned early, other high-energy and age-appropriate breast-milk substitutes need to be readily available. This is generally not the case in many resource-limited settings: childhood stunting is already frequent, and background infant mortality rates related to diarrhea and malnutrition are high. The appropriate nutrients needed by infants and the available foods that provide such nutrients are not well understood by most mothers or primary care health providers. In resource-limited settings, the result is that early weaning often leads to malnutrition and poses additional risks of infection from contaminated food and water [11].

Exclusive breast-feeding is associated with lower rates of HIV-1 transmission than mixed feeding (other liquids or solids in addition to breast milk) [12, 13] and is nutritionally optimal for all infants, regardless of HIV status. Most cultural norms do not support exclusive breast-feeding even in the first few weeks of life, and situations occur frequently in which the mother is transiently not available and the infant is given water or other liquids by caretakers. Despite counseling, exclusive breast-feeding is difficult to implement and requires more encouragement and support for mothers than are routinely available [13]. In Zimbabwe, only 7.6% of mothers reported exclusive breast-feeding for 3 months [13]; in Côte d'Ivoire, only 18% and 10% reported it for 1 and 3 months, respectively [14].

It is of great importance to ascertain whether breast-feeding compromises maternal health in the presence of HIV infection. If a mother dies, the risk of under-five mortality triples [15]. In 2001, in a randomized trial of breast-feeding versus formula feeding, Nduati et al. [16] reported a 3-fold increase in mortality in breast-feeding mothers, raising concerns. Subsequent observational studies did not demonstrate increased maternal mortality, but each study had acknowledged limitations, such as post hoc analysis after the study, the lack of a comparison group, or selection bias [17–19]. However, because maternal mortality rates differ substantially by geographic region (13.8, 17.9, and 42.6 maternal deaths/1000 person-years in South Africa, West Africa, and East Africa, respectively) [19], it is difficult to make comparisons across countries. One also needs to be cognizant that the observations derived from a clinical study may be more favorable than those seen outside the study setting (i.e., in "the real world"). Thus, it is important for prospective studies to directly address this research question.

The study by Otieno et al. [20] that appears in this issue of the Journal is generally reassuring in that breast-feeding was not found to be associated with increased maternal morbidity or mortality when appropriate care was available. Although the prospective study documents a significantly higher rate of decline in CD4 cell count and body mass index during prolonged breast-feeding among mothers, no difference was noted in CD4 cell count decline between HIV-1–infected women who weaned at 6 months and those who never breast-fed. Furthermore, cessation of breast-feeding slowed the CD4 cell count decline, and HIV-1 RNA levels were stable, with no discernable differences between breast-feeding and non–breast-feeding women. Importantly, there was also no significant difference in mortality between breast-feeding and non–breast-feeding mothers, which is consistent with findings from studies in Zambia [18] and South Africa [17]. Thus, the preponderance of evidence indicates that HIV-infected mothers are not compromised by breast-feeding their infants. Fortunately, a variety of appropriate interventions are now available for HIV-infected pregnant women in Nairobi. Women can receive short-course zidovudine during pregnancy, cotrimoxazole prophylaxis as appropriate, and referral for highly active antiretroviral therapy (HAART) when meeting World Health Organization (WHO) guidelines for treatment [21].

As part of the consideration of options for resource-limited settings that could both protect the breast-feeding mother and her HIV-exposed infant, the possible use of maternal HAART is being assessed in 3 ongoing trials in Malawi and Kenya. These studies are testing the efficacy of giving mothers HAART interventions during the first 6 months postpartum, followed by weaning. However, even this strategy has notable adverse events associated with weaning at 6 months. In the Kisumu, Kenya, perinatal trial, in which mothers are given HAART during the last 6 weeks of pregnancy and for 6 months postpartum, preliminary findings demonstrate an increase in serious gastroenteritic adverse events—including growth faltering—among infants after weaning, leading to increased hospitalization rates [22]. Likewise, in a program in Tororo, Uganda, in which breast-feeding women who met the WHO treatment criteria received HAART postpartum for their own care, there was very little infant HIV infection, but 25% of infants died, and infant mortality was inversely correlated with age at weaning [23].

In conclusion, optimizing the health of both HIV-infected mothers and their HIV-exposed infants in resource-limited settings requires careful evaluation of infant-feeding strategies and their consequences. The current recommendation for early weaning may lead to increased infant mortality from causes other than HIV infection, as shown by the Botswana and Uganda studies, whereas prolonged breast-feeding without effective interventions continues to expose infants to HIV infection. Use of maternal HAART during lactation could potentially be protective for women's health and also reduce the risk of infant HIV acquisition by lowering viral load in breast milk. An alternative strategy would be use of an effective vaccine given to perinatally exposed infants that would protect them and allow safe breast-feeding into the second year of life, better ensuring adequate growth and nutrition than the current early weaning strategy. A phase 1 study of a perinatal vaccine has just begun in Uganda, and there are 3 trials currently testing the efficacy of maternal HAART in reducing the risk of transmission during breast-feeding. It is hoped that these ongoing trials will provide clarity as to which strategy is best for reducing breast-milk transmission as well as to what time is optimal for weaning with respect to maximizing HIV-free infant survival and promoting maternal health. In light of current data, WHO recommendations on weaning are being reviewed. Until such time as ongoing trial data are available, ministries of health in resource-limited countries should follow the current WHO recommendations for the prevention of mother-to-child transmission of HIV [21], reserving maternal HAART for those women who meet the WHO treatment guidelines.

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