AEGiS-14IAC: Association of human leukocyte antigens (HLAs) with mother-to-child HIV-1 transmission and HIV-1 specific CD8 T-lymphocyte responses.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Association of human leukocyte antigens (HLAs) with mother-to-child HIV-1 transmission and HIV-1 specific CD8 T-lymphocyte responses.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1383)

Farquhar C, Rowland-Jones S, Mbori-Ngacha D, Oyugi J, Lohman B, Otieno P, Ochieng J, John-Stewart G
University of Washington, Seattle, United States

BACKGROUND: HLA class I and II alleles are determinants of HIV-1 specific CD8 and CD4 T-cell responses. Further characterizing HLAs associated with risk of HIV-1 infection will be important for future epitope-based vaccine development.

METHODS: Blood was collected at birth, 1, 3, 6, 9 and 12 months from infants followed in a Nairobi perinatal HIV-1 study. Molecular HLA typing was performed using PCR-sequence specific primers and HIV-1 specific CD8 T-cell responses were evaluated using ELISpot assays.

RESULTS: HLA typing was performed for 259 infants of whom 43 became HIV-1 infected before month 1 (early) and 7 after month 1 (late). The class I allele A2 was associated with decreased risk of early HIV-1 transmission (HR .5; 95% CI .2-.9; P=.03). Restricting the analysis to breastfeeders, early HIV-1 infection risk was increased for infants with A29 (HR 2.3; 95% CI 1.1-4.9; P=.03) and the class II alleles, DR3 (HR 1.9; P=.07) and DQ6 (HR1.9; P=.09). Late transmission risk was also greater in association with certain HLA alleles, specifically A2 (HR 4; P=.07) and DR14 (HR 9; 95% CI 1.1-78; P=.02). Among infants who remained HIV-1 uninfected, HLAs A3 and A30 increased the likelihood of an infant CD8 T-cell response (P=.007, P=.003 respectively). This was in contrast to A2 and A23 which were associated with not having a CD8 response at age 1 month (P=.07, P=.02 respectively). Homozygosity at the A, B, or C locus was not associated with HIV-1 transmission in this cohort.

CONCLUSION: In this prospective study of class I and II HLAs, we report A29 to be significantly associated with early perinatal HIV-1 infection and DR14 to be associated with late breastmilk transmission. To our knowledge this has not been previously reported. Our data support an association between A2 and decreased early transmission as well as increased late transmission. Late HIV-1 infection among infants with A2 may be attributable to a lower prevalence of HIV-1 specific CD8 T-cell responses.

Keywords: AEGIS, HIV-1, Antigens, CD8, HLA Antigens, T-Lymphocytes, HIV Infections, Mothers, Histocompatibility Testing, Alleles, Polymerase Chain Reaction, Antigens, CD4, Prospective Studies, Child, Human, Infant, transmission, immunology, genetics

020707
ThOrA1383