HV-1-specific cytotoxic T lymphocytes and breast milk HIV-1 transmission.
BACKGROUND
Breast-feeding by infants exposed to human immunodeficiency virus type 1 (HIV-1) provides an opportunity to assess the role played by repeated HIV-1 exposure in eliciting HIV-1-specific immunity and in defining whether immune responses correlate with protection from infection.


METHODS
Breast-feeding infants born to HIV-1-seropositive women were assessed for HLA-selected HIV-1 peptide-specific cytotoxic T lymphocyte interferon (IFN)-gamma responses by means of enzyme-linked immunospot (ELISpot) assays at 1, 3, 6, 9, and 12 months of age. Responses were deemed to be positive when they reached > or = 50 HIV-1-specific sfu/1 x 10(6) peripheral blood mononuclear cells (PBMCs) and were at least twice those of negative controls.


RESULTS
A total of 807 ELISpot assays were performed for 217 infants who remained uninfected with HIV-1 at approximately 12 months of age; 101 infants (47%) had at least 1 positive ELISpot result (median, 78-170 sfu/1 x 10(6) PBMCs). The prevalence and magnitude of responses increased with age (P = .01 and P = .007, respectively); the median log(10) value for HIV-1-specific IFN-gamma responses increased by 1.0 sfu/1 x 10(6) PBMCs/month (P < .001) between 1 and 12 months of age. Of 141 HIV-1-uninfected infants with 1-month ELISpot results, 10 (7%) acquired HIV-1 infection (0/16 with positive vs. 10/125 [8%] with negative ELISpot results; P = .6). Higher values for log(10) HIV-1-specific spot-forming units at 1 month of age were associated with a decreased risk of HIV-1 infection, adjusted for maternal HIV-1 RNA level (adjusted hazard ratio, 0.09 [95% confidence interval, 0.01-0.72]).


CONCLUSIONS
. Breast-feeding HIV-1-exposed uninfected infants frequently had HIV-1-specific IFN-gamma responses. Greater early HIV-1-specific IFN-gamma responses were associated with decreased HIV-1 acquisition.
Department of Paediatrics, University of Nairobi, Nairobi, Kenya. gjohn@u.washington.edu
Grace C
GC
John-Stewart
Dorothy
D
Mbori-Ngacha
Barbara Lohman
BL
Payne
Carey
C
Farquhar
Barbra A
BA
Richardson
Sandra
S
Emery
Phelgona
P
Otieno
Elizabeth
E
Obimbo
Tao
T
Dong
Jennifer
J
Slyker
Ruth
R
Nduati
Julie
J
Overbaugh
Sarah
S
Rowland-Jones
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology / Q000635:transmission*; D005260:Female; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007371:Interferon-gamma / Q000276:immunology; D008895:Milk, Human / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000821:virology*
D007371:Interferon-gamma