HIV-1 Concentrations in Human Breast Milk Before and After Weaning
Science Translational Medicine • 17 Apr 2013 • Vol 5, Issue 181 • p. 181ra51 • DOI: 10.1126/scitranslmed.3005113
Knowing When to Wean
Breast-feeding is essential for infant survival and well-being in the low-resource settings in sub-Saharan Africa most affected by the HIV-1 epidemic. This necessitates breast-feeding by HIV-1–infected mothers despite the 10 to 15% risk of transmitting the infection to the infant via breast milk. Concentrations of HIV-1 in breast milk influence whether the breast-fed infant will acquire infection. Kuhn and colleagues conducted a clinical trial among 958 women in Lusaka, Zambia, to evaluate the safety and efficacy of exclusive breast-feeding followed by abrupt weaning at 4 months as a strategy to prevent postnatal HIV-1 transmission and promote healthy child survival. Women were randomized to wean abruptly at 4 months or to continue breast-feeding for a duration of their own choosing and were followed with their infants from delivery to 24 months postpartum. Infants were tested at regular intervals to determine their HIV-1 status, and concentrations of HIV-1 RNA and DNA were measured in breast milk at 4 and 4.5 months. Two weeks after weaning (4.5 months), HIV-1 concentrations in breast milk were substantially higher than if breast-feeding continued. Among those continuing to breast-feed at 4.5 months, HIV-1 concentrations in milk were lowest if breast-feeding was exclusive. The boost in milk HIV-1 concentrations during weaning counteracted any advantage of shortening the duration of breast-feeding on overall postnatal HIV-1 transmission risks. Breast milk is produced in response to infant suckling. The new data demonstrate that changes in the frequency of suckling as occurs with nonexclusive breast-feeding and at the time of weaning also influence HIV-1 concentrations in breast milk. The results support continuation and possible intensification of maternal antiretroviral drug treatment over the full duration of time when any breast milk exposures are likely to occur after planned weaning.
Abstract
Concentrations of HIV-1 RNA and DNA in mucosal compartments influence the risk of sexual transmission and mother-to-child transmission of HIV-1. Breast milk production is physiologically regulated such that supply is a function of infant demand, but whether demand also influences HIV-1 dynamics in breast milk is unknown. We tested whether minor and major changes in feeding frequency influence breast milk viral concentrations in 958 HIV-1–infected women and their infants followed, for 24 months during a trial in Lusaka, Zambia. Women were randomized to wean abruptly at 4 months or to continue breast-feeding for a duration of their own choosing. Two weeks after breast-feeding cessation (4.5 months), HIV-1 concentrations in breast milk were substantially higher (median RNA, 2708 copies/ml; DNA, 14 copies/ml) than if breast-feeding continued (median RNA, <50 copies/ml; DNA, <1 copy/ml; P < 0.0001). Among those continuing breast-feeding, HIV-1 concentrations in milk were higher if breast-feeding was nonexclusive (median RNA, 293 copies/ml; DNA, 2 copies/ml; P = 0.0006). Elevated milk viral concentrations after stopping breast-feeding explained higher than expected rates of late postnatal HIV transmission in those who weaned early. Changes in the frequency of breast-feeding peri-weaning and with nonexclusive breast-feeding influenced milk viral concentrations. This may explain the reduced risk of HIV-1 transmission associated with exclusive breast-feeding and why early weaning does not achieve the magnitude of HIV prevention predicted by models. Our results support continuation of maternal antiretroviral drug interventions over the full duration of time when any breast milk exposures may occur after planned weaning.
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Supplementary Material
Summary
Fig. S1. Scatter plots showing associations between breast milk HIV-1 RNA concentrations in copies per milliliter, HIV-1 DNA concentration in copies per milliliter, and HIV-1 DNA concentration in copies per 1 million cell equivalents stratified by feeding practice at 4.5 months.
Fig. S2. Flowchart of HIV-infected women who had breast milk HIV measurements.
Breast-feeding and weaning questionnaires
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Science Translational Medicine
Volume 5 | Issue 181
April 2013
April 2013
Copyright
Copyright © 2013, American Association for the Advancement of Science.
Submission history
Received: 9 October 2012
Accepted: 29 March 2013
Acknowledgments
We thank the Zambian families who participated in the research and all the study staff and volunteers. We gratefully acknowledge assistance with aspects of the conduct and write-up of this study from S. Lederman, L. Mofenson, E. Piwoz, D. Raiten, and K. Semrau. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH (HD39611, HD40777, and HD57617). G.M.A. is a recipient of the Elizabeth Glaser Pediatric AIDS Foundation Scientist Award. Author contributions: The study was designed by L.K. and D.M.T. Fieldwork and clinical oversight were provided by M.S., C.K., and M.M. All laboratory work was conducted by G.M.A., D.D., and J.W. The analysis was done by L.K. and H.-Y.K. All authors contributed to the interpretation of the findings and to the write-up of the manuscript. Competing interests: The authors declare that they have no competing interests.
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