Maternal HLA Homozygosity and Mother-Child HLA Concordance Increase the Risk of Vertical Transmission of HIV-1

BackgroundMother-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 MethodsWe 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 ResultsAmong 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 log10 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) ConclusionThe 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