Evidence map›Paper›PMID 28036343›Full record

Trial reportPloS one2016

Concentrations of Pro-Inflammatory Cytokines Are Not Associated with Senescence Marker p16INK4a or Predictive of Intracellular Emtricitabine/Tenofovir Metabolite and Endogenous Nucleotide Exposures in Adults with HIV Infection.

Brian M Maas, Owen Francis, Katie R Mollan, Cynthia Lee, Mackenzie L Cottrell, Heather M A Prince, Craig Sykes, Christine Trezza, Chad Torrice, Nicole White and 4 more

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Cellular Senescence Biomarker p16INK4a+ Cell Burden in Thigh Adipose is Associated With Poor Physical Function in Older Women.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Brian M MaasUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Owen FrancisGillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Katie R MollanSchool of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Cynthia LeeUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Mackenzie L CottrellUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Heather M A PrinceSchool of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Craig SykesUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Christine TrezzaUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Chad TorriceLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Nicole WhiteUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Stephanie MaloneUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Michael G HudgensGillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Norman E SharplessLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Julie B DumondUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
University of North Carolina at Chapel Hill · US

Funding

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
UNC-Duke Collaborative Clinical Pharmacology Postdoctoral Training Program-Evaluation SupplementT32GM086330 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIM L.R. BROUWER, Daniel Gonzalez · 2011 to 2026
$8.5M
The Role of p16INK4 in Mammalian AgingR01AG024379 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HE, SHENGHUI · 2004 to 2019
$4.6M
Optimizing Antiretroviral Use in Aging: Pharmacokinetics, Response, and ToxicityK23AI093156 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DUMOND, JULIE BRUMER · 2011 to 2015
$545k
NIAID NIH HHS K23 AI093156NIAID NIH HHS P30 AI050410NIA NIH HHS R01 AG024379NIGMS NIH HHS T32 GM086330
6 · The paper itself

Abstract

objectivesAs the HIV-infected population ages, the role of cellular senescence and inflammation on co-morbid conditions and pharmacotherapy is increasingly of interest. p16INK4a 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 p16INK4a expression with intracellular metabolite (IM) exposure and endogenous nucleotide concentrations.

methodsSamples from 73 HIV-infected adults receiving daily tenofovir/emtricitabine (TFV/FTC) with either efavirenz (EFV) or atazanavir/ritonavir (ATV/r) were tested for p16INK4a expression, and plasma cytokine and intracellular drug concentrations. Associations between p16INK4a expression and cytokine concentrations were assessed using maximum likelihood methods, and elastic net regression was applied to assess whether cytokines were predictive of intracellular metabolite/endogenous nucleotide exposures.

resultsEnrolled participants had a median age of 48 years (range 23-73). There were no significant associations between p16INK4a expression and cytokines. Results of the elastic net regression showed weak relationships between IL-1Ra and FTC-triphosphate and deoxyadenosine triphosphate exposures, and MIP-1β, age and TFV-diphosphate exposures.

conclusionsIn this clinical evaluation, we found no relationships between p16INK4a 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 p16INK4a association with decreased IM/EN exposures in these HIV-infected participants.

Indexed as

AdultAgedAnti-HIV AgentsBiomarkersCellular SenescenceCyclin-Dependent Kinase Inhibitor p16CytokinesEmtricitabineFemaleHIV InfectionsHumansInflammationMaleMiddle AgedNucleotidesReverse Transcriptase InhibitorsAnti-HIV AgentsBiomarkersCyclin-Dependent Kinase Inhibitor p16CytokinesEmtricitabineNucleotidesReverse Transcriptase InhibitorsRitonavirTenofovir

Identifiers

PMID28036343
PMCPMC5201235
OpenAlexW2569623562

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.