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CTNPT 004: Effects of HLA allele frequencies on HIV disease progression

Trial Results

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Effects of HLA allele frequencies on HIV disease progression and viral load among newly diagnosed HIV infected individuals in Manitoba

Objective

When HIV is acquired it infects the immune cells and causes a decline in a specific type of immune cell called CD4+ T-cells. Variation in the human leucocyte antigen (HLA) gene can influence the rate of CD4 decline. These genes are responsible for cellular molecules that help the immune system distinguish between the body’s own proteins and invading viruses.

The effect of the variations in this gene have been studied in both Caucasian and African patients however very little attention has been paid to those of Aboriginal descent. This population is over-represented among those living with HIV in Canada, particularly in the prairie provinces (Saskatchewan and Manitoba). This study investigated the association between HLA variations and CD4 decline in Manitoba 

Study Population

Two-hundred and ninety-four HIV positive participants were recruited and analyzed for their variation in HLA. Fifty-six recruited participants had the B35 variation of HLA, the B51 variation was present in 58 participants, and 10 individuals had both. One-hundred and eighty other participants were included as a control group (neither B35 nor B51).

Study Design

The study measured the CD4 count at the beginning of the study, the rate of CD4 decline, HIV viral load, and opportunistic infections, among other things. The number of participants whose CD4 cell count fell below 200 cells/mL and/or had opportunistic infections was compared between the groups.

Results

Both HLA B51 and HLA B35 were found to be associated with a progression to AIDS, reaching a CD4 T-cell count of <200 cells/mL, and/or opportunistic infections. The study also found that the HLA B35 was more prevalent in this population than in other groups of people. 

Conclusions

This study identified three major findings: (1) supported the association between the B35 variation and increased disease progression, (2) the B35 variation was found to be overrepresented in the study population, and (3) for the first time the HLA B51 variation was found to be associated with a faster CD4 decline.

Additional Information

Principal Investigators:
Drs. Ken Kasper, Marissa Becker, & Yoav Keynan
University of Manitoba
Ph: 204-787-3633

Publications:

Keynan Y, Becker M, Rueda Z, Bresler K, Kasper K. 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. Infectious Diseases. 2015 Mar;47(7):447–52.

Keynan Y, Rueda ZV, Bresler K, Becker M, Kasper K. HLA B51 is associated with faster AIDS progression among newly diagnosed HIV-infected individuals in Manitoba, Canada. Int J Immunogenet. 2015 Aug;42(5):336–40.

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