New class I and IIHLA alleles strongly associated with opposite patterns of progression to AIDS

The genetics of resistance to infection by HIV-1 cohort consists of 200 slo w and 75 rapid progressors to AIDS corresponding to the extremes of HIV dis ease outcome of 20,000 Caucasians of European descent. A comprehensive anal ysis of HLA class I and class II genes in this highly informative cohort ha s identified HLA alleles associated with fast or slow progression, includin g several not described previously. A quantitative analysis shows an overal l HLA influence independent of and equal in magnitude (for the protective e ffect) to the effect of the CCR5-Delta 32 mutation. Among HLA class I genes , A29 (p = 0.001) and B22 (p < 0.0001) are significantly associated with ra pid progression, whereas B14 (p = 0.001) and C8 (p = 0.004) are significant ly associated with nonprogression, The class I alleles B27, B57, C14 (prote ctive), and C16, as well as B35 (susceptible), are also influential, but th eir effects are less robust. Influence of class II alleles was only observe d for DR11, These results confirm the influence of the immune system on dis ease progression and may have implications on peptide-based vaccine develop ment.