The human leukocyte antigen associations of survival in an acquired immunodeficiency syndrome

An understanding of the molecular basis of immune recognition in human disease is essential for the development of antigen specific immunotherapy. Here, a new method for unambiguous human leukocyte antigen typing (HLA) is assessed and followed by an immunogenetic study exploring the association of HLA with disease outcomes in a group of adolescents who have survived with untreated, perinatal human immunodeficiency virus type-1 (HIV-1) infection. The new method for high-resolution, unambiguous, mono-allelic genotyping of HLA-B and C alleles was tested on a subset of samples from a cohort of Zimbabwean Shona adolesents. Three novel HLA-C alleles were described and named by the World Health Organisation Nomenclature Committee for Factors of the HLA System. Next, the association of HLA in HIV-1 disease progression was assessed in the Shona adolescents perinatally infected with the virus. Previous reports have shown that African infants with vertically-acquired HIV-1 infection progress rapidly, with only 50% surviving beyond two years in the absence of treatment. Recent reports, however, have described a substantial burden of older children living with untreated vertically-acquired HIV-1 infection in Southern Africa. The immunological and genetic factors associated with long-term survival following vertical infection are poorly understood. Medium-tohigh resolution HLA typing was performed on DNA samples obtained from a cohort of presumed vertically HIV-1 infected children and age-matched uninfected controls in Harare, Zimbabwe. Overall, 93 HLA class I alleles were detected in the study population with a significant enrichment of HLA-C*08:02 and -C*08:04 in the HIV-1 infected longterm survivor group. Conversely, HLA-A*02:01, -A*34:02 and -B*58:02 were overrepresented in the uninfected control group. Together, these preliminary studies serve as a common starting point to identify pathways of immune recognition inherent in disease susceptibility and survival.