HLA and AIDS: a cautionary tale

The human major histocompatibility complex HLA has been implicated repeatedly as a regulator of the outcome of HIV exposure and infection. A new study of long-term survivors who naturally depress HIV-1 replication and avoid the signs of AIDS for years after infection suggests that homozygosity for a group of HLA-B locus alleles termed Bw4 confers resistance, ostensibly by regulating natural killer cell–ligand interactions. However, close inspection of the accumulated evidence raises some questions and urges validation of the potential Bw4 effects in additional studies.