1 / 21

Maternal HLA-A*2301 is Associated with Increased Vertical HIV-1 Transmission

Maternal HLA-A*2301 is Associated with Increased Vertical HIV-1 Transmission. Romel D. Mackelprang University of Washington International AIDS Conference August 6, 2008. HLA Class I Molecules. Encoded by the HLA-A, B and C genes Most polymorphic genes found in humans

raanan
Télécharger la présentation

Maternal HLA-A*2301 is Associated with Increased Vertical HIV-1 Transmission

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Maternal HLA-A*2301 is Associated with Increased Vertical HIV-1 Transmission Romel D. Mackelprang University of Washington International AIDS Conference August 6, 2008

  2. HLA Class I Molecules • Encoded by the HLA-A, B and C genes • Most polymorphic genes found in humans • Found on all leukocytes • Critical component of cellular immune responses • Present peptides to CD8+ T cells

  3. HLA Class I Function

  4. HLA Class I Function

  5. HLA Class I Function

  6. Maternal HLA and HIV-1 • HLA alleles influence susceptibility to HIV-1 infection and progression • Maternal HLA might also be associated with transmission risk • Via influence on maternal HIV-1 progression • Selection of virulent/infectious viral isolates • Proxy for infant alleles

  7. Specific Aims • Examine associations between maternal HLA class I alleles and vertical HIV-1 transmission • Early (in utero, peripartum, and via early breastfeeding) • Late (via breastfeeding)

  8. Recruitment and Follow-up

  9. Recruitment and Follow-up

  10. Recruitment and Follow-up

  11. Statistical Methods Logistic regression for early transmission Cox regression for late transmission Adjusted for maternal plasma HIV-1 viral load at 32-weeks gestation Alleles with => 10% allele frequency Bonferroni correction for each locus

  12. Description of the Cohort

  13. HLA Alleles 88 unique alleles (33 A, 44 B, 11 C alleles) 20 alleles expressed by >10%

  14. Early Transmission

  15. Early Transmission

  16. Early Transmission • A*2301 • Unadjusted OR=3.21 (1.42, 7.27), p=0.005 • Significant after Bonferroni correction (p<0.006) • Carriers had higher plasma VL • 5.03 versus 4.65 log10 copies/ml, p=0.03 • Similar trend for VL in other compartments • Viral load adjusted OR= 3.07 (1.26, 7.51), p=0.014 • Possible effect beyond influence on VL

  17. Late transmission • A*0201 = increased late transmission risk • 6 (12%) mothers with allele transmitted • 5 (3%) mothers without allele transmitted • HR=4.41 (1.37, 14.18), p=0.01 • Evidence that HLA-Bw4 motif = decreased transmission risk • aHR=0.5 (0.3, 0.9), p=0.02 • Small numbers, interpret with caution

  18. Maternal A*2301 is associated with increased transmission • OR≈3 before and after adjusting for VL • Possible effect beyond influence on VL • Infant A*23 not associated with susceptibility • Consistent with non-MTCT studies • ≈3-fold risk of seroconversion among Kenyan CSWs (MacDonald, 1998) • Faster disease progression among children in the US (Chen, 1997) • A*23 = faster disease progression, ↑ risk of Kaposi’s Sarcoma (Kaslow, 1996; Mann, 1990; Prince, 1984)

  19. Conclusion Data emphasize complex roles immunogenetic factors play in HIV-1 transmission Strengthen evidence that HLA should be considered when developing vaccines and other interventions

  20. Acknowledgements • Oxford • Sarah Rowland-Jones • Fred Hutchinson • Julie Overbaugh • Sandy Emery • Dana Panteleeff • University of Nairobi • Dorothy Mbori-Ngacha • • Rose Bosire • • Elizabeth Obimbo • • Phelgona Otieno • • Dalton Wamalwa • • Christine Gichuhi • • Jennifer Mabuka • • Grace Wariua Special thanks to the women and infants who participated. • University of Washington • Carey Farquhar • Grace John-Stewart • Barbra Richardson • Barbara Lohman-Payne • Jenn Slyker • NCI-Frederick • Mary Carrington • Xiaojiang Gao Funding sources NICHD, NCI, FIC

More Related