Homozygosity for a conserved Mhc class II DQ-DRB haplotype is associated with rapid disease progression in simian immunodeficiency virus-infected macaques: Results from a prospective study

In human immunodeficiency virus type 1 (HIV-1)-infected individuals, diseas e progression varies considerably. This is also observed after experimental infection of macaques with simian immunodeficiency virus (SIV). Major hist ocompatibility complex (MHC) genes may influence disease progression in bot h species. Homozygosity for Mhc-Mamu (Macaca mulatta)-DQB1*0601 was previou sly identified to be associated with rapid disease progression in SIV-infec ted macaques. To validate the association of this genotype with disease pro gression, a prospective study was carried out. Six unrelated monkeys homozy gous for Mamu-DQB1*0601 and DRB1*0309-DRB*W201 and 6 heterozygous monkeys w ere infected with SIVmac. Five of the homozygous and only 1 of the heterozy gous monkeys died rapidly after infection, with manifestations of AIDS. The se results were validated by a retrospective survival analysis of 71 SIV-in fected monkeys. The identified DQ-DRB genotype is frequent among monkeys of different breeding colonies and allows a fairly reliable selection before infection of monkeys predisposed for rapid disease progression.