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Session 51 Poster Session Impact of Host Genetics on Viral Transmission and Disease Progression Session Time: 4:30-6:30 pm Room 4E-F

319-W. Association of HLA-B22 with Increased Plasma HIV-1 RNA Concentration and Accelerated Progression to AIDS in Caucasian Cohorts M. T. Dorak*1, J. Tang1, S. Tang1, R. Coutinho2, J. J. Goedert3, R. Detels4, and R. A. Kaslow1 1Univ. of Alabama, Birmingham; 2Amsterdam Cohort Study, The Netherlands; 3NCI, NIH, Bethesda, MD; and 4MultiCtr. AIDS Cohort Study Background: An association of alleles in the HLA-B22 group (B*54, *55 and *56) with faster HIV disease progression has been suggested. B22 group alleles belong to the B7 supertype, as do B*35 and the closely related B*53, also associated with faster progression. B7 supertype alleles preferentially bind CTL peptides containing proline at anchor residue position 2 but have shown different affinities for position 9 residues. We examined the B22 influence on early HIV RNA level and subsequent disease progression in infected Caucasian men from 3 cohorts. Methods: Multicenter AIDS Cohort Study, DC Gay, and Amsterdam Cohort Study subjects (n=716) with closely estimated onset of infection were HLA typed at A, B, and C loci by standard molecular methods. Log10 mean plasma HIV RNA concentration (viral load=VL in copies/mL) was measured (Roche Amplicor/Monitor) for 380 participants in successive intervals during 42 months after seroconversion and analyzed by general linear model techniques. We compared time to AIDS in B22-positive (n=32) and -negative (n=684) men by Kaplan-Meier and Cox regression methods. Adjustments were made for other established genetic determinants. Results: During each post-conversion interval, higher mean VLs (4.56-4.90) were observed for men with than men without a B22 subtype (4.30-4.36; p=0.002-0.14). B22 carriers progressed significantly faster than non-carriers in each separate cohort and in aggregate (adjusted relative hazard=1.98, p=0.001). The effects were independent of age and presence of B*35/B*53 and other accepted genetic markers of progression in Caucasians. Other alleles of the B7 supertype have not shown such relationships. Conclusions: Associations of B22 alleles with higher VL and faster disease progression resemble those reported for B*35 and B*53 alleles and contrast with effects of other members of the B7 supertype. Systematic dissection of the similarities and differences in HIV epitope binding among members of the B7 supertype at the molecular level may reveal important mechanisms of viral evasion of or escape from cell-mediated immunity.

©2002 9th Conference on Retroviruses and Opportunistic Infections