IL-6 Predicts p16INK4a Expression, Intracellular Tenofovir/Emtricitabine Exposure, and Endogenous Nucleotide Pools in Adults with HIV
Public Deposited- Last Modified
- February 26, 2019
- Creator
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Lee, Cynthia
- Affiliation: Eshelman School of Pharmacy
- Abstract
- Objectives: It was recently found that p16INK4a, a marker for aging and cellular senescence, is associated with lower intracellular concentrations of endogenous nucleotides and nucleos(t)ide reverse transcriptase inhibitors (NRTIs). This study expands on these findings by determining whether markers of inflammation are predictive of p16INK4a expression, intracellular metabolite exposure, or endogenous nucleotide concentrations. Methods: Samples from HIV-infected adults receiving daily tenofovir/emtricitabine (TFV/FTC) with either efavirenz (EFV) or atazanavir/ritonavir (ATV/r) were tested for p16INK4a expression, plasma cytokine concentrations, and intracellular drug concentrations. Elastic net regression was used to identify cytokines that were predictive of p16INK4a expression and intracellular metabolite/endogenous nucleotide exposures. These outcomes were each compared between groups with detectable versus undetectable levels of predictive cytokines using a Wilcoxon rank-sum test. Results: Enrolled participants had a median age of 48 years (range 23 - 73). Results of the elastic net regression determined that individuals with detectable interleukin-6 (IL-6) concentrations were predicted to have elevated p16INK4a expression and lower exposure to tenofovir diphosphate (TFV-dp), emtricitabine triphosphate (FTC-tp), and their respective endogenous nucleotides, deoxyadenosine triphosphate (dATP) and deoxycytidine triphosphate (dCTP). Conclusions: Elevated concentrations of IL-6 have been associated with frailty, morbidity, and mortality in individuals with HIV. Our findings suggest that IL-6 affects cellular senescence, NRTI pharmacokinetics, and endogenous nucleotide pools in an aging HIV population.
- Date of publication
- spring 2016
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright
- Note
- Funding: None
- Advisor
- Dumond, Julie
- Degree
- Doctor of Pharmacy
- Honors level
- Highest Honors
- Degree granting institution
- University of North Carolina at Chapel Hill
- Extent
- 16
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