Transmission of cell-free and cell-associated HIV-1 through breast-feeding.
BACKGROUND
Transmission through breast-feeding is an important cause of infant HIV-1 infections in developing countries; however, its mechanism remains largely unknown. We have explored the association between cell-free virus (CFV) and cell-associated virus (CAV) levels in breast milk (BM), as reflected by viral RNA and proviral DNA, respectively, and the risk of infant HIV-1 infection after 6 weeks postpartum.


METHODS
Sixty-one HIV-positive mothers who transmitted HIV-1 by BM were matched to 61 HIV-positive nontransmitting mothers based on their infant's age at sample collection. CFV and CAV were quantified in a single milk specimen per mother preceding the infant's first HIV-positive result.


RESULTS
After adjusting for maternal CD4 cell counts and disease stage, each 10-fold increase in CFV or CAV load was associated with an almost 3-fold increase in BM transmission. Whereas CAV load was predictive of transmission before and after 9 months postpartum, CFV was a significant predictor of transmission occurring only after 9 months. Phylogenetic analyses of the C2 to C5 env region showed that 85% of infants (11 of 13 infants) harboring viruses that clustered with CFV in their mother's milk were infected after 9 months postpartum.


CONCLUSIONS
A reduction in milk CAV and CFV loads might significantly decrease HIV-1 transmission by breast-feeding.
Koulinska
Irene N
IN
Harvard School of Public Health AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Villamor
Eduardo
E
Chaplin
Beth
B
Msamanga
Gernard
G
Fawzi
Wafaie
W
Renjifo
Boris
B
Essex
Max
M
D000328:Adult; D001942:Breast Feeding / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002474:Cell-Free System; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D015686:Gene Products, env / Q000235:genetics; D006679:HIV Seropositivity / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008895:Milk, Human / Q000166:cytology / Q000821:virology*; D008969:Molecular Sequence Data; D010919:Placebos; D012044:Regression Analysis; D013636:Tanzania; D014815:Vitamins / Q000008:administration & dosage / Q000627:therapeutic use*
D015686:Gene Products, env; D010919:Placebos; D014815:Vitamins