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.
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.
From the 1 Manitoba HIV Program , Winnipeg, MB , Canada.
Yoav
Y
Keynan
Marissa
M
Becker
Zulma
Z
Rueda
Kim
K
Bresler
Ken
K
Kasper
D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005787:Gene Frequency; D015658:HIV Infections / Q000208:ethnology / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015235:HLA-B Antigens / Q000235:genetics*; D015797:HLA-B35 Antigen; D059949:HLA-B51 Antigen / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D008350:Manitoba / Q000208:ethnology; D012189:Retrospective Studies; D019562:Viral Load
D015235:HLA-B Antigens; D015797:HLA-B35 Antigen; D059949:HLA-B51 Antigen
CD4 decline; HIV disease progression; HLA homozygocity; HLA-B