Skip Navigation LinksHome > September 24, 2013 - Volume 27 - Issue 15 > Toll-like receptor variants are associated with infant HIV-1...
doi: 10.1097/QAD.0b013e3283629117
Epidemiology and Social

Toll-like receptor variants are associated with infant HIV-1 acquisition and peak plasma HIV-1 RNA level

Beima-Sofie, Kristin M.a,e; Bigham, Abigail W.h; Lingappa, Jairam R.c,e,f; Wamalwa, Daltonj; Mackelprang, Romel D.e; Bamshad, Michael J.f,g; Maleche-Obimbo, Elizabethj; Richardson, Barbra A.d,e,i; John-Stewart, Grace C.b,c,e,d

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Objective: We evaluated the association of single nucleotide polymorphisms (SNPs) in TLRs with infant HIV-1 acquisition and viral control.

Design: Infant HIV-1 outcomes were assessed in a Kenyan perinatal HIV-1 cohort.

Methods: Infants were genotyped for six candidate and 118 haplotype-tagging polymorphisms in TLRs 2, 3, 4, 7, 8, and 9, MYD88 and TIRAP. Cox proportional hazards and linear regression were performed to assess associations with time to HIV-1 acquisition, time to infant mortality, and peak viral load.

Results: Among 368 infants, 56 (15%) acquired HIV-1 by month 1 and 17 (4.6%) between 1 and 12 months. Infants with the TLR9 1635A (rs352140) variant were more likely to acquire HIV-1 by 1 month [hazard ratio = 1.81, 95% confidence interval (CI) = 1.05–3.14, P = 0.033] and by 12 months (hazard ratio = 1.62, CI = 1.01–2.60, P = 0.044) in dominant models adjusted for maternal plasma HIV-1 RNA level and genetic ancestry. Among 56 infants infected at 1 month of age or less, at least one copy of the TLR9 1635A allele was associated with a 0.58 log10 copies/ml lower peak viral load (P = 0.002). Female infants with at least one copy of the TLR8 1G (rs3764880) variant had a 0.78 log10 copies/ml higher peak viral load (P = 0.0009) and having at least one copy of the C allele for a haplotype tagging TLR7 variant (rs1634319) was associated with a 0.80 log10 copies/ml higher peak viral load in female infants (P = 0.0003).

Conclusion: In this African perinatal cohort, we found several TLR polymorphisms associated with HIV-1 acquisition and progression. Defining mechanisms for these TLR associations may inform HIV-1 prevention strategies that leverage innate responses.

© 2013 Lippincott Williams & Wilkins, Inc.


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