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Overview: Balancing Infant Feeding Options
HIV InSite's Coverage of the 14th Conference on Retroviruses and Opportunistic Infections
Elise Arrivé, MD; Valériane Leroy, MD; Unité INSERM 593, Equipe VIH Afrique, Institut de Santé Publique, Epidémiologie et Développement (ISPED), Université Victor Segalen, Bordeaux, France

Published March 23, 2007
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Overview
Presentations
Zambia Exclusive Breastfeeding Study
Diarrhea in Uninfected Infants of HIV-Infected Mothers
Severe Diarrhea and Gastroenteritis Associated with Early Weaning
Implications for HIV Prevention Strategies
Take Home Message

Overview

Studies presented at CROI tended to reexamine the benefit of early cessation of breast-feeding and replacement feeding among populations in which the safety of such intervention is uncertain.

Presentations

Zambia Exclusive Breastfeeding Study

Abstract: Sinkala M, Kuhn L, Kankasa C, et al. No Benefit of Early Cessation of Breastfeeding at 4 Months on HIV-free Survival of Infants Born to HIV-infected Mothers in Zambia: The Zambia Exclusive Breastfeeding Study. Abstract 74.

Description: In the Zambia Exclusive Breastfeeding Study (ZEBS), 958 women were randomly assigned to one of two groups. One group included those who breast-fed exclusively, with abrupt cessation at 4 months, whereas the other group continued breast-feeding until the mothers chose to wean. All women intending to breast-feed were eligible for enrollment, and all received single-dose nevirapine. All enrolled women were counseled to exclusively breast-feed their infants for the first 4 months of life. The main end point was HIV-free survival at 24 months of age.

Results: There was no significant difference in HIV-free survival between the two groups at 24 weeks. Among the infants surviving without HIV infection at 4 months, 17% of 329 infants in the abrupt cessassion group and 19% of 331 infants in the prolonged breast-feeding group had HIV infection or had died by 24 months (p = 0.21). Among 153 infants with HIV infection by 4 months, there was a significant benefit with continued breast-feeding. Mortality was higher at 12 months in the abrupt cessassion group (57%) than in the prolonged breast-feeding group (29%) (p = 0.01). Among children of asymptomatic mothers with CD4 counts of >350 cells/µL, HIV-free survival rates were better in those who continued to breast-feed than in those who were weaned early.

Diarrhea in Uninfected Infants of HIV-Infected Mothers

Abstract: Kourtis, A, Fitzgerald D, Hyde L, et al. Diarrhea in Uninfected Infants of HIV-infected Mothers Who Stop Breastfeeding at 6 Months: The BAN Study Experience. Abstract 772.

Description: In the ongoing Breastfeeding Antiretrovirals Nutrition (BAN) study, conducted in Malawi, mothers and infants are randomized to a maternal or an infant antiretroviral regimen or to standard of care during breast-feeding. In addition, mothers are randomized to receive or not receive a nutritional supplement during breast-feeding. They are encouraged to breast-feed exclusively and to wean when the infants reach 6 months of age.

Results: To date, 771 HIV-uninfected infants have been enrolled. Among 225 uninfected infants who survived to 28 weeks, the frequency of diarrhea rose around the time of breast-feeding cessation, as well as during the rainy season. However, the diarrhea-associated mortality rate was low.

Severe Diarrhea and Gastroenteritis Associated with Early Weaning

The following studies found an increase of severe diarrhea and gastroenteritis compared with historical controls when early cessation of breast-feeding was promoted among HIV-exposed children between 3 and 6 months of age.

Abstract: Kafulafula G, Thigpen M, Hoover D, et al. Post-weaning Gastroenteritis and Mortality in HIV-uninfected African Infants Receiving Antiretroviral Prophylaxis to Prevent MTCT of HIV-1. Abstract 773.

Description: This study provides comparisons of mortality rates and gastroenteritis-related mortality of infants followed within the ongoing Post-Exposure Prophylaxis for Infants (PEPI) study and the Nevirapine/AZT (NVAZ) study (2000-2003), both controlled open-label Phase III trials conducted in Malawi. In the PEPI trial, mothers are encouraged to breast-feed exclusively for 6 months with abrupt weaning, whereas no abrupt cessation of breast-feeding was recommended in the NVAZ trial.

Results: Overall mortality and gastroenteritis-related mortality after 6 months of age was higher among participants in the PEPI study than among participants in the NVAZ study.



Abstract: Thomas T, Masaba R, van Eijk A, et al. Rates of Diarrhea Associated with Early Weaning among Infants in Kisumu, Kenya. Abstract 774.

Description: This study provides a comparison of rates of diarrhea events during the first year of life among HIV-negative infants in the ongoing Kisumu Breastfeeding Study (KiBS), in which cessation of breast-feeding at 6 months is encouraged, and those in a study of vertical transmission conducted in Kenya from 1996 to 2001, in which no nutrition intervention was provided. In the vertical transmission study, infants were fed according to traditional feeding practices, which often involve the introduction of complementary foods and water by 2 to 3 months of age and continued breast-feeding beyond 12 months.

Results: Overall diarrhea incidence during the first 12 months of life was significantly lower in the KiBS group than in the vertical transmission group. KiBS diarrhea rates peaked during the weaning period at 6 and 7 months and then declined, in contrast to vertical transmission rates, which remained elevated after 3 months. Serious diarrhea resulting in hospitalization peaked in the KiBS group at 6 months and was significantly higher overall than in the vertical transmission group.



Abstract: Onyango C, Mmiro F, Bagenda D, et al. Early Breastfeeding Cessation among HIV-exposed Negative Infants and Risk of Serious Gastroenteritis: Findings from a Perinatal Prevention Trial in Kampala, Uganda. Abstract 775.

Description: In this study, rates of gastroenteritis events and mortality pre- and post-cessation of breast-feeding in infants were compared among those enrolled in an immunoglobulin/antiretroviral (HIVIGLOB) trial and the HIVNET 012 trial, both conducted in Uganda. In the first trial, which started in 2004, with enrollment completed in 2006, median age of breast-feeding cessation was 3 months, whereas it was 8.7 months in the second trial, which was conducted in the late 1990s.

Results: Serious infant gastroenteritis-related morbidity in the first year, rate of gastroenteritis-related morbidity at 3 months after cessation of breast-feeding, and cumulative infant mortality throughout the first 9 months of life were higher in the HIVIGLOB trial (in which infants were weaned at around 3 months) than in the HIVNET 012 trial (in which infants were weaned later).

Limitations: Suggesting that early and abrupt breast-feeding cessation increase morbidity and mortality among infants, these results should be interpreted with caution, as the data being compared were taken from different studies conducted at different time periods, and the comparisons were not adjusted.

Implications for HIV Prevention Strategies

Abstract: Creek T, Arvelo W, Kim A, et al. A Large Outbreak of Diarrhea among Non-breastfed Children in Botswana, 2006--Implications for HIV Prevention Strategies and Child Health. Abstract 9.

Description: This presentation summarizes the results of an investigation conducted by the U.S. Centers for Disease Control and Prevention (CDC) into an outbreak of diarrhea and malnutrition among young children in Botswana during 2006 that coincided with heavy rains and widespread water contamination. A national program for prevention of mother-to-child transmission (PMTCT) of HIV in Botswana supplies formula foods for free, but does not conduct postnatal follow-up.

Results: Among 153 diarrhea inpatients <5 years old, 65% had HIV-infected mothers, many developed severe acute malnutrition during or after diarrhea, and 22% died. None of the infants who were breast-fed died. Most of the deaths occurred in children who were not HIV infected and were formula fed in the context of the PMTCT program. A review of the child health cards of 20 infants who died documented inadequate formula supply.

Take Home Message

The studies presented at CROI regarding infant feeding question the safety of early and abrupt breast-feeding cessation among HIV-infected women and the use of formula given systematically without careful and close postnatal monitoring in resource-limited settings.

The studies suggest that prolonged breast-feeding is beneficial for HIV-infected children and could lead to higher HIV-free survival than shorter breast-feeding for children whose mothers are asymptomatic and have high CD4 cell counts. All these studies also serve as a reminder that the period of breast-feeding cessation is a critical time for morbid events and deaths.

The main recommendations raised during this conference include the following:

  • Closely monitor all alternatives to prolonged breast-feeding, including the period of breast-feeding cessation.
  • Consider precisely and adequately the safety of formula feeding, based on individual parameters and also community parameters such as health services, nutrition support, and postnatal counseling.
  • Continue exclusive breast-feeding beyond 6 months if the child is HIV infected.
  • Conduct further research on PMTCT interventions during breast-feeding.

These recommendations support the consensus statement of the World Health Organization HIV and Infant Feeding Technical Consultation, held October 25-27, 2006, in Geneva. [PDF, 102K]