Polymorphisms in the Toll-Like Receptor (TLR9) 1635 locus have been associated with HIV-1 acquisition and progression. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) acquisition were compared between Kenyan HIV-exposed infants by 1635 genotype. Having 1 or more copies of the 1635A allele was associated with increased CMV acquisition in HIV-infected infants (42% vs 11%, p = 0.03) and increased risk of EBV acquisition in HIV-exposed uninfected infants (HR = 4.2, p = 0.02) compared to 1635GG. Additionally, 1635A was associated with 0.4 log10 copies/ml lower median EBV levels in HIV-infected infants (p = 0.03). These data suggest a potentially important role for this locus in primary herpesvirus infection.