Concentrations of Pro-Inflammatory Cytokines Are Not Associated with Senescence Marker p16.sup.INK4a or Predictive of Intracellular Emtricitabine/Tenofovir Metabolite and Endogenous Nucleotide Exposures in Adults with HIV Infection

As the HIV-infected population ages, the role of cellular senescence and inflammation on co-morbid conditions and pharmacotherapy is increasingly of interest. p16.sup.INK4a expression, a marker for aging and senescence in T-cells, is associated with lower intracellular concentrations of endogenous n...

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Bibliographic Details
Published in:PloS one 2016-12, Vol.11 (12), p.e0168709
Main Authors: Maas, Brian M, Francis, Owen, Mollan, Katie R, Lee, Cynthia, Cottrell, Mackenzie L, Prince, Heather M. A, Sykes, Craig, Trezza, Christine, Torrice, Chad, White, Nicole, Malone, Stephanie, Hudgens, Michael G, Sharpless, Norman E, Dumond, Julie B
Format: Article
Language:English
Subjects:
Analysis
Cytokines
Gene expression
Genetic aspects
HIV infections
Inflammation
Metabolites
Nucleotides
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Summary:As the HIV-infected population ages, the role of cellular senescence and inflammation on co-morbid conditions and pharmacotherapy is increasingly of interest. p16.sup.INK4a expression, a marker for aging and senescence in T-cells, is associated with lower intracellular concentrations of endogenous nucleotides (EN) and nucleos(t)ide reverse transcriptase inhibitors (NRTIs). This study expands on these findings by determining whether inflammation is contributing to the association of p16.sup.INK4a expression with intracellular metabolite (IM) exposure and endogenous nucleotide concentrations. Enrolled participants had a median age of 48 years (range 23-73). There were no significant associations between p16.sup.INK4a expression and cytokines. Results of the elastic net regression showed weak relationships between IL-1Ra and FTC-triphosphate and deoxyadenosine triphosphate exposures, and MIP-1[beta], age and TFV-diphosphate exposures. In this clinical evaluation, we found no relationships between p16.sup.INK4a expression and cytokines, or cytokines and intracellular nucleotide concentrations. While inflammation is known to play a role in this population, it is not a major contributor to the p16.sup.INK4a association with decreased IM/EN exposures in these HIV-infected participants.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0168709