Rapid human immunodeficiency virus disease progression is associated with human leukocyte antigen-B homozygocity and human leukocyte antigen-B51 in a cohort from Manitoba, Canada

Abstract

Background: Human immunodeficiency virus type 1 (HIV-1) infection is associated with variable rates of disease progression, influenced by the quality of CD8 T-lymphocyte response, which is determined by human leukocyte antigen (HLA) I alleles. Some individuals progress slowly and maintain viral control, while at the opposite end of the spectrum some individuals endure a faster progression with rapid CD4 decline. We sought to determine the role of HLA-B allele frequency on rapid HIV disease progression. It was hypothesized that rapid progression is associated with the presence of high allele frequency of HLA-B35 and HLA-B homozygocity. Methods: This retrospective cohort study was conducted in the Manitoba HIV Program, Health Sciences Centre, a tertiary care facility in Winnipeg, Manitoba, Canada. We defined a set of new criteria to describe a subset of individuals with the most rapid HIV disease progression, and collected demographic, clinical, laboratory (CD4 count, viral load) and HLA data on a subset of 20 individuals meeting these criteria. Results: Among those individuals who display extreme rapid progression, an overrepresentation of Aboriginal ethnicities, high frequencies of HLA-B35 and significantly higher rates of HLA-B51, as well as a very high rate of homozygocity for HLA-B alleles, were observed. Conclusions: Individuals with the most rapid disease progression have higher rates of HLA-B homozygocity, HLA-B51 alleles and higher viral loads than those with normal progression rates. This group, at the extreme end of the spectrum of progression, should be targeted for early treatment.