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Kristin Beima-Sofie , MPH, PhDc AIDS 2012 Abstract # MOPDA0101 Monday July 23, 2012

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, PhDc AIDS 2012 Abstract # MOPDA0101 Monday July 23, 2012.

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Kristin Beima-Sofie , MPH, PhDc AIDS 2012 Abstract # MOPDA0101 Monday July 23, 2012

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  1. 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 KristinBeima-Sofie, MPH, PhDc • AIDS 2012 Abstract #MOPDA0101 Monday July 23, 2012

  2. Toll-like Receptor (TLR) Polymorphisms and Infant HIV Acquisition and Disease Progression 396 infants • 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 79 HIV infected 317 HIV uninfected Lower peak VL Decreased mortality Higher peak VL Increased mortality

  3. TLR9 Variant is Associated with HIV Acquisition Acquisition • 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

  4. 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 p=0.0021 p=0.0009 p=0.0003 • Mortality • No SNPs were significantlyassociated with mortality • *First study to identify variations in TLR7 and TLR8 that are associated with peak VL in HIV-infected infants

  5. 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

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