This study explores whether MHC genes affect manifestations of opportunistic infections in HIV patients not treated with highly active antiretoviral therapy (HAART) and immunopathologic responses to preexisting infections in patients who achieved immune reconstitution following HAART (i.e., "immune restoration diseases" or IRD). HLA-B27 and B17 were relatively rare in all HIV patients, but no HLA-B alleles significantly affected cytomegalovirus (CMV) or Mycobacterium avium complex (MAC) disease in patients who had not received HAART. However coexpression of alleles previously defined as the 44.1 ancestral haplotype (HLA-A2, -B44, and DR I) was more common in the MAC and CMV patients. After HAART, HLA-B44 and (HLA-A2, -B44, -DR4) were found in 66% and 33%, respectively, of patients who experienced an IRD manifested as CMV retinitis and/or encephalomyelitis. This was confirmed by examination of microsatellite alleles, where the C1_2_5 locus in the class I region was most concordant with the 44.1 haplotype in the patients. HLA-B44 was not associated with IRD initiated by Mycobacterium sp, cutancous VZV or HSV, or HCV infections, suggesting distinct pathologic mechanisms are responsible. CMV retinicis/encephalomyelitis IRD patients had marginally lower pretreatment CD4 T-cell counts, but indices of immune reconstitution were similar in all groups and independent of HLA-B44. (C) American Society for Histocompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.