title: Breast Milk of HIV-Positive Mothers Has Potent and Species-Specific In Vivo HIV-Inhibitory Activity.
abstract: Despite the nutritional and health benefits of breast milk, breast milk can serve as a vector for mother-to-child HIV transmission. Most HIV-infected infants acquire HIV through breastfeeding. Paradoxically, most infants breastfed by HIV-positive women do not become infected. This is potentially attributed to anti-HIV factors in breast milk. Breast milk of HIV-negative women can inhibit HIV infection. However, the HIV-inhibitory activity of breast milk from HIV-positive mothers has not been evaluated. In addition, while significant differences in breast milk composition between transmitting and nontransmitting HIV-positive mothers have been correlated with transmission risk, the HIV-inhibitory activity of their breast milk has not been compared. This knowledge may significantly impact the design of prevention approaches in resource-limited settings that do not deny infants of HIV-positive women the health benefits of breast milk. Here, we utilized bone marrow/liver/thymus humanized mice to evaluate the in vivo HIV-inhibitory activity of breast milk obtained from HIV-positive transmitting and nontransmitting mothers. We also assessed the species specificity and biochemical characteristics of milk's in vivo HIV-inhibitory activity and its ability to inhibit other modes of HIV infection. Our results demonstrate that breast milk of HIV-positive mothers has potent HIV-inhibitory activity and indicate that breast milk can prevent multiple routes of infection. Most importantly, this activity is unique to human milk. Our results also suggest multiple factors in breast milk may contribute to its HIV-inhibitory activity. Collectively, our results support current recommendations that HIV-positive mothers in resource-limited settings exclusively breastfeed in combination with antiretroviral therapy.
  
  
  OBJECTIVE
  Approximately 240,000 children become infected with HIV annually, the majority via breastfeeding. Despite daily exposure to virus in breast milk, most infants breastfed by HIV-positive women do not acquire HIV. The low risk of breastfeeding-associated HIV transmission is likely due to antiviral factors in breast milk. It is well documented that breast milk of HIV-negative women can inhibit HIV infection. Here, we demonstrate, for the first time, that breast milk of HIV-positive mothers (nontransmitters and transmitters) inhibits HIV transmission. We also demonstrate that breast milk can prevent multiple routes of HIV acquisition and that this activity is unique to human milk. Collectively, our results support current guidelines which recommend that HIV-positive women in resource-limited settings exclusively breastfeed in combination with infant or maternal antiretroviral therapy.
authors: Division of Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
authors: Angela
authors: A
authors: Wahl
authors: Division of Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
authors: Caroline
authors: C
authors: Baker
authors: Division of Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
authors: Rae Ann
authors: RA
authors: Spagnuolo
authors: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors: Lisa W
authors: LW
authors: Stamper
authors: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors: Genevieve G
authors: GG
authors: Fouda
authors: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors: Sallie R
authors: SR
authors: Permar
authors: Department of Human Evolutionary Biology, Harvard University, Cambridge, Massachusetts, USA.
authors: Katie
authors: K
authors: Hinde
authors: Gertrude H. Sergievsky Center and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
authors: Louise
authors: L
authors: Kuhn
authors: Division of Neonatal Medicine and Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of California, San Diego, San Diego, California, USA.
authors: Lars
authors: L
authors: Bode
authors: Department of Pediatrics, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.
authors: Grace M
authors: GM
authors: Aldrovandi
authors: Division of Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA victor_garcia@med.unc.edu.
authors: J Victor
authors: JV
authors: Garcia
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control* / Q000635:transmission*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control* / Q000706:statistics & numerical data; D008253:Macaca mulatta; D051379:Mice; D008895:Milk, Human / Q000737:chemistry* / Q000276:immunology; D013045:Species Specificity; D015024:Zambia