Consistent associations of HLA class I and II and transporter gene products with progression of human immunodeficiency virus type 1 infection in homosexual men

Polymorphic products of genes in the HLA region contributing to variability in the course of human immunodeficiency virus type 1 (HIV-1) infection wer e identified by screening 375 Caucasian seroconverters who were aggregated from 3 cohorts. AIDS-free time was related to numerous (15) class I alleles , alone or in conjunction with transporter protein variants, to homozygosit y at the A or B locus, and to alleles of two class II haplotypes. A prognos tic scoring algorithm derived from the 3 cohorts captured multiple HLA cont ributions to protection or to risk (relative hazard = 0.57-60 per unit incr ease in score, all P << .001). The impact of HLA was strong and appeared in dependent of the effects of chemokine receptor/ligand polymorphisms and ant iretroviral treatment. The algorithm also predicted divergent rates of CD4( +) cell decline in 2 other groups, totaling 227 seropositive persons (P = . 06 - < .001), Confirmation of these relationships should encourage investig ation of HIV-1 antigen processing and presentation mediated by polymorphism s in the HLA region.