HIV-1-specific cytotoxic T lymphocytes and breast milk HIV-1 transmission
John-Stewart GC., Mbori-Ngacha D., Payne BL., Farquhar C., Richardson BA., Emery S., Otieno P., Obimbo E., Dong T., Slyker J., Nduati R., Overbaugh J., Rowland-Jones S.
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)-γ 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 ≥50 HIV-1-specific sfu/1 × 106peripheral 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 ̃12 months of age; 101 infants (47%) had at least 1 positive ELISpot result (median, 78-170 sfu/1 × 106 PBMCs). The prevalence and magnitude of responses increased with age (P = .01 and P = .007, respectively); the median log10 value for HIV-1-specific IFN-γ responses increased by 1.0 sfu/1 × 106PBMCs/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 log10HIV-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-γ responses. Greater early HIV-1-specific IFN-γ responses were associated with decreased HIV-1 acquisition. © 2009 by the Infectious Diseases Society of America.