AEGiS-14IAC: HLA-B locus alleles influence the risk of mother to child transmission of HIV-1.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

HLA-B locus alleles influence the risk of mother to child transmission of HIV-1.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. LbPeA9005)

Winchester R, Pitt J, Magder L, Charurat M, Ott J, Landay A, Read JS, Shearer W, Handelsman E, Luzuriaga K, Hillyer G, Blattner W
Columbia University, New York, United States

BACKGROUND: While certain HLA-B alleles are associated with the rate of HIV disease progression, their role in transmission is not known.

METHODS: To determine the association of HLA-B alleles with maternal-infant transmission of HIV-1, 83 transmitting and 163 non-transmitting mother infant pairs in the WITS cohort were matched for ethnicity and study site. DNA from cryopreserved lymphocytes was used for sequence-based HLA-B allele typing.

RESULTS: The distribution of HLA-B alleles differed in cases and controls. Transmitting women more likely had B*1302 (p=.02), B*3501 (p=.01) and B*3503 (p=.04). The association of B*3501 and transmission was highest among African-Americans (OR 8.8, p=.01). HLA-B*5001, found primarily in Hispanics, was associated with increased transmission, p=.01. B*3501 was associated with transmission in women with low (<10,000 copies/ml) (OR 12.5, p=.02) but not high (>10,000 copies/ml) viral load. (OR 2.6 p=.24). Among women without B*3501or B*3503, (removed to eliminate confounding) B*5301 was associated with decreased transmission (OR 0.3, p=0.025). B*5001 and B*4901 were marginally associated with increased and decreased transmission respectively (p=.071 and .06). Protective alleles had stronger effect in conditions of high viral load. Infant HLA-B alleles had no significant effect on transmission.

CONCLUSIONS: The association of maternal B*3501 with transmission and B*5301 with protection differs from the associations reported for disease progression, suggesting the two involve distinct mechanisms. The protective allele B*4901 differs from the risk allele B*5001 by the same 5 amino acids that the protective allele B*5301 differs from the risk allele B*3501. This five amino acid motif both encodes Bw4 specificity (the NK receptor ligand) and affects the F pocket that binds the C terminus of the antigenic peptide (CD8 cytotoxic T cell antigen binding), suggesting roles for innate and adaptive immunity in transmission.

Keywords: AEGIS, HIV-1, HLA-B Antigens, Alleles, Viral Load, Acquired Immunodeficiency Syndrome, Disease Progression, Mothers, T-Lymphocytes, Cytotoxic, Case-Control Studies, Child, Infant, Human, Female, transmission, immunology, genetics

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