Elizabeth J McFarland1,2, Tina M Powell3, Carolyne Onyango-Makumbi4, Weiming Zhang5, Kelsey Melander6, Prossy Naluyima7, Samuel Okurut7, Michael A Eller8,9, Mary Glenn Fowler10,4, Edward N Janoff6,2,11. 1. Departments of 1 Pediatrics and. 2. Mucosal and Vaccine Research Program Colorado, Infectious Diseases. University of Colorado-Anschutz Medical Campus, Aurora, and. 3. Departments of 1Pediatrics and. 4. Makerere University-Johns Hopkins University Research Collaboration, and. 5. Department of Biostatistics and Informatics, Colorado School of Public Health, and. 6. Medicine. 7. Makerere University Walter Reed Project, Kampala, Uganda. 8. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Springs. 9. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, and. 10. Johns Hopkins University School of Medicine, Baltimore, Maryland. 11. Denver Veterans Affairs Medical Center, Colorado.
Abstract
Background: Among infants exposed to human immunodeficiency virus (HIV) type 1, mixed breastfeeding is associated with higher postnatal HIV-1 transmission than exclusive breastfeeding, but the mechanisms of this differential risk are uncertain. Methods: HIV-1-exposed Ugandan infants were prospectively assessed during the first year of life for feeding practices and T-cell maturation, intestinal homing (β7hi), activation, and HIV-1 coreceptor (CCR5) expression in peripheral blood. Infants receiving only breast milk and those with introduction of other foods before 6 months were categorized as exclusive and nonexclusive, respectively. Results: Among CD4+ and CD8+ T cells, the expression of memory, activation, and CCR5 markers increased rapidly from birth to week 2, peaking at week 6, whereas cells expressing the intestinal homing marker increased steadily in the central memory (CM) and effector memory T cells over 48 weeks. At 24 weeks, when feeding practices had diverged, nonexclusively breastfed infants showed increased frequencies and absolute counts of β7hi CM CD4+ and CD8+ T cells, including the HIV-1-targeted cells with CD4+β7hi/CCR5+ coexpression, as well as increased activation. Conclusions: The T-cell phenotype associated with susceptibility to HIV-1 infection (CCR5+, gut-homing, CM CD4+ T cells) was preferentially expressed in nonexclusively breastfed infants, a group of infants at increased risk for HIV-1 acquisition.
Background: Among infants exposed to human immunodeficiency virus (HIV) type 1, mixed breastfeeding is associated with higher postnatal HIV-1 transmission than exclusive breastfeeding, but the mechanisms of this differential risk are uncertain. Methods:HIV-1-exposed Ugandan infants were prospectively assessed during the first year of life for feeding practices and T-cell maturation, intestinal homing (β7hi), activation, and HIV-1 coreceptor (CCR5) expression in peripheral blood. Infants receiving only breast milk and those with introduction of other foods before 6 months were categorized as exclusive and nonexclusive, respectively. Results: Among CD4+ and CD8+ T cells, the expression of memory, activation, and CCR5 markers increased rapidly from birth to week 2, peaking at week 6, whereas cells expressing the intestinal homing marker increased steadily in the central memory (CM) and effector memory T cells over 48 weeks. At 24 weeks, when feeding practices had diverged, nonexclusively breastfed infants showed increased frequencies and absolute counts of β7hi CM CD4+ and CD8+ T cells, including the HIV-1-targeted cells with CD4+β7hi/CCR5+ coexpression, as well as increased activation. Conclusions: The T-cell phenotype associated with susceptibility to HIV-1 infection (CCR5+, gut-homing, CM CD4+ T cells) was preferentially expressed in nonexclusively breastfed infants, a group of infants at increased risk for HIV-1 acquisition.
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