Concordance of human leukocyte antigen haplotype-sharing, CD4 decline and AIDS in hemophilic siblings. Multicenter Hemophilia Cohort and Hemophilia Growth and Development Studies.
OBJECTIVE
To assess the association between human leukocyte antigen (HLA) haplotypes and the incidence rates of CD4 decline to < 20% and to AIDS.


METHODS
Retrospective cohort study of 95 HIV-1-infected hemophilic sibling pairs.


METHODS
HLA haplotype-sharing between siblings was assigned on the basis of serologic typing of HLA class I alleles and molecular typing of HLA class II alleles. Concordance of time to CD4 decline to < 20% and to AIDS within and between sibling pairs was assessed by analysis of variance models and calculations of intraclass correlation coefficients. The age-adjusted relative risks of these two endpoints for unique class II haplotypes were determined from proportional hazards models.


RESULTS
Sibling pairs sharing one or two haplotypes were significantly concordant in CD4 decline and AIDS status within 5 years of seroconversion. No concordance was found in pairs sharing zero haplotypes. At 6-10 years after seroconversion, significant concordance of these two endpoints was also observed in the pairs sharing one haplotype. The concordant results were not explained by the use of zidovudine within the pairs. Among the individuals in this cohort, the relative hazards for CD4 decline to < 20% and for AIDS were significantly elevated for one class II haplotype (DQB1*0501, DQA1*0101, DRB1*0101). In addition, the risk for AIDS was significantly increased for two other class II haplotypes (DQB1*0603, DQA1*0103, DRB1*1300, DRB3*0202 and DQB1*0301, DQA1*0501, DRB1*1400, DRB3*0202) and significantly decreased for one haplotype (DQB1*0302, DQA1*0301, DRB1*0401, DRB4*0101).


CONCLUSIONS
These data demonstrate that HIV-1 disease progression is associated with the genes in the major histocompatibility complex that regulate the host's immune response.
Kroner
B L
BL
Epidemiologic and Medical Studies Program, Research Triangle Institute, Rockville, MD 20852, USA.
Goedert
J J
JJ
Blattner
W A
WA
Wilson
S E
SE
Carrington
M N
MN
Mann
D L
DL
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D000367:Age Factors; D000704:Analysis of Variance; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006679:HIV Seropositivity; D015497:HIV-1; D006239:Haplotypes; D006467:Hemophilia A / Q000150:complications*; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D000949:Histocompatibility Antigens Class II / Q000097:blood*; D006801:Humans; D015994:Incidence; D009679:Nuclear Family; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015215:Zidovudine / Q000627:therapeutic use
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D015215:Zidovudine