2nd National Conference Human Retroviruses and Related Infections Washington, DC - January 29 - February 2, 1995

Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 20)

Kaslow RA, Mann D, Apple R, Carrington M, Munoz A, Park L, Detels R, Rinaldo C, Phair J, Goedert J, Saah A, for the Multicenter AIDS Cohort Study (MACS) and the DC Gay Cohort (DCG)
National Institutes of Health, Bethesda, MD 20892

OBJECTIVE: To examine associations between HLA gene products and rate of progression of HIV-1 infection.

METHODS: We HLA- typed 241 homosexual seroconverters using microcytotoxicity for alleles at class I (A,B) and PCR-based methods both for detecting alleles at class II (DRB1,DQA1,DQB1) and for determining TAP1 & TAP2 variants. 137 men developed AIDS (100 in less than 7 yrs) and 104 remained AIDS-free for approximately 6-13 yrs (99 for ≥ 7 yrs after conversion. Stratifications and Cox regressions including interactions were used to analyze the data.

RESULTS: We identified 6 A/B alleles that, alone or together with certain TAP variants, were favorably (+1) associated with time to AIDS; we also found 7 A/B alleles plus 4 DRB1- DQA1-DQB1 haplotypes that, alone or together with certain TAP variants, were unfavorably (-1) associated. The HLA profile (sum of integers representing HLA gene products) showed a strong (p<0.001) relation to AIDS-free interval:

DISCUSSION: Specific combinations of interacting HLA class I, class II and TAP gene products appear to impact heavily on the course of HIV-1 infection. Confirmation of these effects on the natural history will have broad implication for care and vaccine development.

Keywords: Acquired Immunodeficiency Syndrome, Alleles, Disease Progression, HIV Infections, HLA Antigens, HLA-A Antigens, HLA-B Antigens, HLA-C Antigens, HLA-DP Antigens, HLA-DQ Antigens, HLA-DR Antigens, Haplotypes, Humans, Male, genetics, immunology

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1995-01-29
20

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