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 were 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 homozygosity at the A or B locus, and to alleles of two class II haplotypes. A prognostic scoring algorithm derived from the 3 cohorts captured multiple HLA contributions to protection or to risk (relative hazard=0.57-60 per unit increase in score, all P<<.001). The impact of HLA was strong and appeared independent of the effects of chemokine receptor/ligand polymorphisms and antiretroviral 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 investigation of HIV-1 antigen processing and presentation mediated by polymorphisms in the HLA region.
Keet
I P
IP
Municipal Health Service, Amsterdam, The Netherlands. Reneke@hcrg.nl
Tang
J
J
Klein
M R
MR
LeBlanc
S
S
Enger
C
C
Rivers
C
C
Apple
R J
RJ
Mann
D
D
Goedert
J J
JJ
Miedema
F
F
Kaslow
R A
RA
D000328:Adult; D000465:Algorithms; D017951:Antigen Presentation; D018791:CD4 Lymphocyte Count; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology*; D006679:HIV Seropositivity; D015497:HIV-1; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D018451:Homosexuality, Male; D006720:Homozygote; D006801:Humans; D008297:Male
D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II