Immunogenetics of CD4 lymphocyte count recovery during antiretroviral therapy: An AIDS Clinical Trials Group study.

Haas DW, Geraghty DE, Andersen J, Mar J, Motsinger AA, D'Aquila RT, Unutmaz D, Benson CA, Ritchie MD, Landay A, AIDS Clinical Trials Group
J Infect Dis. 2006 194 (8): 1098-107

PMID: 16991084 · DOI:10.1086/507313

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 > 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- alpha , Bcl-2-interacting molecule (Bim), interleukin (IL)-15, and IL-15 receptor alpha chain (IL-15R alpha ) were associated with the magnitude of the increase in CD4 lymphocyte count, as were haplotypes in genes encoding interferon- alpha , IL-2, and IL-15R alpha (P < .05, for each). Multifactor dimensionality reduction identified a gene-gene interaction between IL-2/IL-15 receptor common beta chain and IL-2/IL-7/IL-15 receptor common gamma 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.

MeSH Terms (19)

Adult Antiretroviral Therapy, Highly Active Apoptosis Regulatory Proteins CD4 Lymphocyte Count CD4-Positive T-Lymphocytes Female HIV Infections Humans Interleukin-2 Male Membrane Glycoproteins Polymorphism, Genetic Puerto Rico Receptors, Interleukin-2 Receptors, Interleukin-15 Retrospective Studies TNF-Related Apoptosis-Inducing Ligand Tumor Necrosis Factor-alpha United States

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