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Background: Although evidence supports a relationship between human immunodeficiency virus (HIV)-1 exposure and HIV-1-specific CD8(+) T cell responses, studies have not demonstrated a direct association between the quantity of HIV-1 to which a person is exposed and the presence or absence of a response., Methods: From 1999 to 2005, maternal HIV-1 RNA levels were measured in blood, cervical secretions, and breast milk at delivery and 1 month after delivery. HIV-1-specific interferon (IFN)-γ Elispot assays were conducted to determine infant CD8(+) T-cell responses at 3 months of age., Results: Among 161 infants tested with Elispot assays, 23 (14%) had positive results. Mothers whose infants had a positive assay had higher breast milk HIV-1 RNA levels at month 1 compared with mothers whose infants had negative Elispot assays (3.1 vs 2.5 log(10) copies/mL; P = .017). Female infants were also more likely to have positive Elispot assays than male infants (P = .046), and in multivariate analyses, both female sex and high breast milk HIV-1 levels remained important predictors of a positive response (P = .022 and P = .015, respectively)., Conclusions: Exposure to breast milk HIV-1 and sex were associated with development of HIV-1-specific CD8(+) T-cell responses in infants. These data support a role for mucosal exposure via the oral route in induction of systemic HIV-1-specific cellular immunity.

Summary Among 288 HIV-1-infected, breastfeeding women who received zidovudine prophylaxis and were followed with their infants in Nairobi, we found no associations between maternal genetic polymorphisms in CCR5 (59029G/A, 59353T/C, 59356T/C, 59402G/A), RANTES (-403G/A) and SDF-1 (3'801G/A) and mother-to-child HIV-1 transmission; plasma, cervical and breastmilk viral loads; or breastmilk chemokine concentrations.

Background: Mother-child human leukocyte antigen (HLA) concordance and maternal HLA homozygosity may increase the risk of vertical transmission of human immunodeficiency virus type 1 (HIV-1) risk by reducing infant immune responses., Methods: We analyzed mother-child HLA concordance and maternal HLA homozygosity in a Kenyan perinatal cohort receiving antenatal zidovudine. HLA concordance was scored as the number of shared class I alleles, and relative risk estimates were adjusted for maternal HIV-1 load., Results: Among 277 mother-infant pairs, HIV-1 transmission occurred in 58 infants (21%), with in utero transmission in 21 (36%), peripartum transmission in 26 (45%), and transmission via breast-feeding in 11 (19%). With increased concordance, we observed a significant increase in the risk of transmission overall (adjusted hazard ratio [aHR], 1.3 [95% confidence interval {CI}, 1.0-1.7]; P = .04 in utero (adjusted odds ratio, 1.72 [95% CI, 1.0-1.7]; P = .04), and via breast-feeding (aHR, 1.6 [95% CI, 1.0-2.5]; P = .04). Women with homozygosity had higher plasma HIV-1 RNA levels at 32 weeks of gestation (5.1 vs. 4.8 log(10) copies/mL; P = .03) and an increased risk of transmission overall (aHR, 1.7 [95% CI, 1.1-2.7]; P = .03) and via breast-feeding (aHR, 5.8 [95% CI, 1.9-17.7]; P = .002)., Conclusion: The risks of overall, in utero, and breast milk HIV-1 transmission increased with HLA concordance and homozygosity. The increased risk may be due to reduced alloimmunity or less diverse protective immune responses.