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

TitleImmunogenetics of CD4 lymphocyte count recovery during antiretroviral therapy: An AIDS Clinical Trials Group study.
Publication TypeJournal Article
Year of Publication2006
AuthorsHaas DW, Geraghty DE, Andersen J, Mar J, Motsinger AA, D'Aquila RT, Unutmaz D, Benson CA, Ritchie MD, Landay A
Corporate AuthorsAIDS Clinical Trials Group
JournalJ Infect Dis
Volume194
Issue8
Pagination1098-107
Date Published2006 Oct 15
ISSN0022-1899
KeywordsAdult, 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-15, Receptors, Interleukin-2, Retrospective Studies, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha, United States
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 > 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.

DOI10.1086/507313
Alternate JournalJ. Infect. Dis.
PubMed ID16991084
Grant List303-0804 / / PHS HHS / United States
AI13656 / AI / NIAID NIH HHS / United States
AI25859-19 / AI / NIAID NIH HHS / United States
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AI50410 / AI / NIAID NIH HHS / United States
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ISL 204IC005 / / PHS HHS / United States
RR00044 / RR / NCRR NIH HHS / United States
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