Immunogenetics of CD4 lymphocyte count recovery during antiretroviral therapy: An AIDS clinical trials group study

David W. Haas, Daniel E. Geraghty, Janet Andersen, Jessica Mar, Alison A. Motsinger, Richard T. D'Aquila, Derya Unutmaz, Constance A. Benson, Marylyn D. Ritchie, Alan Landay

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

During antiretroviral therapy, CD4 lymphocyte count increases are modest in some patients despite virologic control. We explored whether polymorphisms in genes important for T cell expansion, survival, and apoptosis are associated with the magnitude of CD4 lymphocyte count recovery during antiretroviral therapy. We studied treatment-naive individuals who achieved sustained control of plasma viremia (<400 HIV-1 RNA copies/mL) for at least 48 weeks after initiation of antiretroviral therapy and compared genotypes among individuals who had an increase of either <200 or ≥200 CD4 cells/mm3 from baseline. A total of 137 single-nucleotide polymorphisms across 17 genes were characterized in 873 study participants. In multivariate analyses that controlled for clinical variables, polymorphisms in genes encoding tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), TNF-α, Bcl-2-interacting molecule (Bim), interleukin (IL)-15, and IL-15 receptor a chain (IL-15Rα) were associated with the magnitude of the increase in CD4 lymphocyte count, as were haplotypes in genes encoding interferon-α, IL-2, and IL-15Rα- (P<.05, for each). Multifactor dimensionality reduction identified a gene-gene interaction between IL-2/IL-15 receptor common β chain and IL-2/IL-7/IL-15 receptor common γ chain. Immune recovery during antiretroviral therapy is a complex phenotype that is influenced by multiple genetic variants. Future studies should validate these tentative associations and define underlying mechanisms.

Original languageEnglish (US)
Pages (from-to)1098-1107
Number of pages10
JournalJournal of Infectious Diseases
Volume194
Issue number8
DOIs
StatePublished - Oct 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Haas, D. W., Geraghty, D. E., Andersen, J., Mar, J., Motsinger, A. A., D'Aquila, R. T., Unutmaz, D., Benson, C. A., Ritchie, M. D., & Landay, A. (2006). Immunogenetics of CD4 lymphocyte count recovery during antiretroviral therapy: An AIDS clinical trials group study. Journal of Infectious Diseases, 194(8), 1098-1107. https://doi.org/10.1086/507313