title: Infective and anti-infective properties of breastmilk from HIV-1-infected women.
abstract: Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly by cell-to-cell contact. We postulated that transmission of HIV-1 through breastmilk could be favoured by the presence of infected cells, by deficiency of anti-infective substances in breastmilk, or both factors. 215 HIV-1-infected women were enrolled at delivery in Kigali, Rwanda; milk samples were collected 15 days, 6 months, and 18 months post partum. HIV-1 IgG, secretory IgA, and IgM were assayed by western blot, for the latter two after removal of IgG with protein G. In the 15-day and 6-month samples, we sought viral genome in milk cells by a double polymerase chain reaction with three sets of primers (gag, pol, and env). HIV-1 infection in the offspring was defined according to serological and clinical criteria. At 15 days, 6 months, and 18 months post partum, HIV-1 specific IgG was detected in 95%, 98%, and 97% of breastmilk samples, IgA in 23%, 28%, and 41%, and IgM in 66%, 78%, and 41%. In children who survived longer than 18 months, the probability of infection was associated with lack of persistence of IgM and IgA in their mothers' milk (adjusted chi 2 for trend, p = 0.01 for IgM and p = 0.05 for IgA). The presence of HIV-1-infected cells in the milk 15 days post partum was strongly predictive of HIV-1 infection in the child, by both univariate (p < 0.05) and multivariate analysis (p = 0.01). The combination of HIV-1-infected cells in breastmilk and a defective IgM response was the strongest predictor of infection. HIV-1 infection in breastfed children born to infected mothers is associated with the presence of integrated viral DNA in the mothers' milk cells. IgM and IgA anti-HIV-1 in breastmilk may protect against postnatal transmission of the virus.
authors.affiliation: National AIDS Control Programme, AIDS Reference Laboratory, Kigali, Rwanda.
authors.forename: P
authors.initials: P
authors.lastname: Van de Perre
authors.forename: A
authors.initials: A
authors.lastname: Simonon
authors.forename: D G
authors.initials: DG
authors.lastname: Hitimana
authors.forename: F
authors.initials: F
authors.lastname: Dabis
authors.forename: P
authors.initials: P
authors.lastname: Msellati
authors.forename: B
authors.initials: B
authors.lastname: Mukamabano
authors.forename: J B
authors.initials: JB
authors.lastname: Butera
authors.forename: C
authors.initials: C
authors.lastname: Van Goethem
authors.forename: E
authors.initials: E
authors.lastname: Karita
authors.forename: P
authors.initials: P
authors.lastname: Lepage
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D001942:Breast Feeding; D016516:CD4-CD8 Ratio; D004279:DNA, Viral / Q000737:chemistry; D005260:Female; D015483:HIV Antibodies / Q000737:chemistry; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D008895:Milk, Human / Q000737:chemistry / Q000276:immunology / Q000382:microbiology*; D015999:Multivariate Analysis; D009419:Nerve Tissue Proteins; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012432:Rwanda / Q000453:epidemiology; D015996:Survival Rate; D013997:Time Factors
chemical_list: D004279:DNA, Viral; C029152:G-substrate; D015483:HIV Antibodies; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009419:Nerve Tissue Proteins