The human leukocyte antigen (HLA)-B22 serogroup - which consists of the alleles B*54, B*55, and B*56 - has been associated with rapidly progressive disease in white patients with human immunodeficiency virus (HIV) infection. Subjects from 3 cohorts of men who have sex with men (N = 671), all of whom experienced HIV-1 seroconversion at roughly the same time, were molecularly typed at HLA-A, -B, and -C loci. Mean HIV RNA loads during early HIV infection were higher in B22-positive men than in B22-negative men (difference, 0.481 log10 HIV RNA copies/mL; 95% confidence interval [CI], 0.156-0.806 log10 HIV RNA copies/mL; P = .004). Independent of accepted markers of progression, time-to-AIDS was shorter in B22-positive seroconverters (adjusted hazard ratio, 1.98; 95% CI, 1.27-3.10; P = .003). White B22 serogroup alleles (B*55 and *56) appear to predispose to unfavorable outcome of HIV infection as strongly as some or all B*35 and B*53 alleles. This finding may have greater implications for Asians, because the marker frequency for B22 is higher among Asians than among whites (∼10% vs. ∼4%).