Abstracts 55

B-5.2 #97

CONCORDANCE OF AIDS IN HEMOPHILIC HLA SIBSHIPS SHARING HLA HAPLOTYPES. M O'Donnel! I, B Kroner 2, J Goedert 3, M Carrington I, D Mann 4, Program Resources Inc/DynCorp I, Research Triangle Institute!, Viral Epidemiology Branch ° , Laboratory of Viral Carcinogenesis", Rockville and Frederick, MD.

The major histocompatibility complex (MHC) encodes products that regulate the immune response. Furthermore the target cells for HIV-I infection are those whose interactions are regulated by these products (HLA). To demonstrate the possible influence of the MHC on the natural history of HIV-I infection we determined HLA class I alleles (serologically) and HLA class II (molecular techniques) in 92 HIV-I infected hemophilic sibships. HLA haplotypes were determined based on allele sharing and haplotype sharing status (assigned 0,1 or 2). Expected AIDS hazard for each individual was determined and inter-class correlation (IC) was compared by ANOVA between and within sibships. At 10 years of followup, sibs sharing no haplotypes had no AIDS concordance (IC= -0.193, sibs sharing I haplotype had IC of AIDS incidence of 0.28. The IC was the highest in sibs sharing 2 haplotypes (0.42). This data indicates that the MHC plays a substan- tive role in disease progression and outcome in HIV-1 infection.

B-5.2 #98

HLA ASSOCIATIONS IN LONG TERM SURVIVORS OF HIV-I INFECTION. A Hardinq I, M Carrington I, M O'Donnell I, D Marti I, JJ Goedert 2, DL Mann~ Program Resources Inc/D~nCorp I, Viral Epidemiology Branch 2, Laboratory of Viral Carcinogenesis 3 NCI, Rockville and Frederick, MD.

HIV-I infection leads to progressive loss of CD4+ T cell to a stage of immune paralysis and AIDS. To date the factors (host, viral) that influence variabi l i ty in the disease free interval with infection have not been determined. We have HLA typed, (class I by serology, class I I , TAPI, TAP2 by molecular techniques) 117 HIV-I seropositive gay men that have been followed since 1982. At 4 years, 17 had developed AIDS, at 7 years 50, and at present 71. We compared HLA allele frequencies in disease-free groups at various time intervals using 2x2 tables, Fisher's exact test and non-parametric statist ical methods. During the f i r s t 5 years of followup, HLA-Bw4 was stat is t ical ly more frequent in individuals without AIDS than in those with AIDS. However, at present no differences in frequency were observed. DQAI*0102 was present equally in both groups at 4 years, in 48% of AIDS patients vs 30% no- AIDS at 7 years (p=0.054), and 48% of AIDS vs 19% no-AIDS at present (>10 years; p=O.O04). When combined with DQBI*0602, significant differences in frequencies were found in AIDS (37%) vs no-AIDS (17%) (p=0.033) at present. Addition of DRBI alleles associated with these DQ alleles did not show any differences between the groups at any time period. In contrast, an entire haplotype DQAI*OSOI-DQBI*O2OI- DRBI*O3OI-DRB3*0101 was more frequent in the long term group surviving without AIDS (31%) at the present compared to the frequency of this haplotype in the AIDS group (7%). These data indicate a substantive role for HLA in rates of disease progression in HIV-I infection.