Association of HLA genotype with T-cell activation in human immunodeficiency virus (HIV) and HIV/ hepatitis c virus-coinfected women

Background. Global immune activation and HLA alleles are each associated with the pathogenesis of human immunodeficiency virus (HIV) and hepatitis C virus. Methods. We evaluated the relationship between 44 HLA class I and 28 class II alleles and percentages of activated CD8 (CD8⁺CD38⁺DR⁺) and CD4 (CD4⁺CD38⁺DR⁺) T cells in 586 women who were naive to highly active antiretroviral therapy. We used linear generalized estimating equation regression models, adjusting for race/ethnicity, age, HIV load, and hepatitis C virus infection and controlling for multiplicity using a false discovery rate threshold of 0.10. Results. Ten HLA alleles were associated with CD8 and/or CD4 T-cell activation. Lower percentages of activated CD8 and/or CD4 T cells were associated with protective alleles B*57:03 (CD8 T cells, −6.6% [P =.002]; CD4 T cells, −2.7% [P =.007]), C*18:01 (CD8 T cells, −6.6%; P <.0008) and DRB1*13:01 (CD4 T cells, −2.7%; P <.0004), and higher percentages were found with B*18:01 (CD8 T cells, 6.2%; P <.0003), a detrimental allele. Other alleles/allele groups associated with activation included C*12:03, group DQA1*01:00, DQB1*03:01, DQB1*03:02, DQB1*06:02, and DQB1*06:03. Conclusion. These findings suggest that a person's HLA type may play a role in modulating T-cell activation independent of viral load and sheds light on the relationship between HLA, T-cell activation, immune control, and HIV pathogenesis.