Toll-like Receptor (TLR) 9 variant is associated with mother-to-child

transmission (MTCT) of HIV-1 and TLR9 and TLR8 variants are associated with

peak viral load in HIV-1 infected infants

Kristin Beima-Sofie, MPH, PhDcAIDS 2012 Abstract #MOPDA0101

Monday July 23, 2012

Washington D.C., USA, 22-27 July 2012www.aids2012.org

Toll-like Receptor (TLR) Polymorphisms and Infant HIV Acquisition and Disease

Progression

TLRs Critical proteins of the innate

immune system involved in pathogen recognition

Study Population Historical MTCT cohort from

Nairobi Kenya

Genotyping 6 candidate SNPs and 118 haplotype-tagging SNPs

396 infants

317 HIV uninfecte

d

Lower peak VLDecreased mortality

Higher peak VLIncreased mortality

79 HIV infected

Washington D.C., USA, 22-27 July 2012www.aids2012.org

TLR9 Variant is Associated with HIV AcquisitionAcquisition

15% of infants HIV positive by month 1 4.8% acquired HIV between month 1 and months 12

One or more copies of TLR9 1635A variant is significantly associated with acquisition by month 1 and month 12

First study to identify a variant in TLR9 that is associated with HIV acquisition in an African MTCT cohort

Washington D.C., USA, 22-27 July 2012www.aids2012.org

TLR7, TLR8 and TLR9 variants are associated with Peak Viral Load

Peak Viral Load Mean peak viral load in HIV infected infants: 6.8 log10 c/ml Novel TLR7 and candidateTLR8 and TLR9 variants are associated with peak

VL

*First study to identify variations in TLR7 and TLR8 that are associated with peak VL in HIV-infected infants

Mortality No SNPs were significantly associated with mortality

p=0.0009p=0.0021 p=0.0003

Washington D.C., USA, 22-27 July 2012www.aids2012.org

Acknowledgements

We gratefully acknowledge and appreciate the participation of study participants and study

staff from Nairobi, Kenya

NIH Funding Sources R21 AI073115 TL1 TR000422 R01 HD3412 R24 TW007988