Evidence map›Paper›PMID 25763783›Full record

ArticleJournal of acquired immune deficiency syndromes (1999)2015

Reduced immune activation during tenofovir-emtricitabine therapy in HIV-negative individuals.

Jose R Castillo-Mancilla, Amie Meditz, Cara Wilson, Jia-Hua Zheng, Brent E Palmer, Eric J Lee, Edward M Gardner, Sharon Seifert, Becky Kerr, Lane R Bushman and 2 more

2 registry-linked trialsAbstract read
In one paragraph

Article in Journal of acquired immune deficiency syndromes (1999), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.8field-weighted citation impact, top 29% 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.

NCT01040091 phase1completednot on this map

Cellular Pharmacology of Tenofovir and Emtricitabine for HIV Prophylaxis (Cell Prep)

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2009 to 2014Enrolled34ConditionsHIV InfectionsArmsEmtricitabine (FTC), Tenofovir disoproxil fumarate (TDF), Efavirenz (EFV), Truvada
NCT04405271 phase3terminatednot on this mapstarted 2020, after this paper: background citation

Randomized, Double-blind, Placebo-controlled Trial of TAF/FTC for Pre-exposure Prophylaxis of COVID-19 in Healthcare Workers (CoviPrep Study)

TypeinterventionalSponsorHospital Italiano de Buenos AiresRan2020 to 2020Enrolled1,378ConditionsHealthcare Workers, COVID-19, SARS-CoV 2ArmsEmtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet, Placebo
3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 26 citations in OpenAlex.

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  6. Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
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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

12 authors at 2 institutions in 1 country.

Jose R Castillo-Mancilla*Department of Medicine, Division of Infectious Diseases, School of Medicine, University of Colorado AMC, Aurora, CO; †Beacon Center for Infectious Disease, Boulder, CO; ‡Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado AMC, Aurora, CO; §Department of Medicine, Division of Allergy and Clinical Immunology, School of Medicine, University of Colorado AMC, Aurora CO; ‖Department of Medicine, Denver Health Medical Center, Denver, CO; and ¶Department of Biostatistics and Bioinformatics, Colorado School of Public Health, University of Colorado-AMC, Aurora, CO.
Amie Meditz
Cara Wilson
Jia-Hua Zheng
Brent E Palmer
Eric J Lee
Edward M Gardner
Sharon Seifert
Becky Kerr
Lane R Bushman
Samantha MaWhinney
Peter L Anderson
University of Colorado Denver · USUniversity of Montana · US

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025780 · NCRR · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2008 to 2011
$61.3M
Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Cellular pharmacology of tenofovir and emtricitabine for HIV prophylaxisU01AI084735 · NIAID · UNIVERSITY OF COLORADO DENVER · PI ANDERSON, PETER L. · 2009 to 2012
$4.2M
Quantifying Drug Adherence and Drug Exposure to Antiretroviral TherapyK23AI104315 · NIAID · UNIVERSITY OF COLORADO DENVER · PI CASTILLO-MANCILLA, JOSE RAMON · 2013 to 2017
$910k
NCATS NIH HHS UL1 TR001082NCRR NIH HHS UL1 RR025780NIAID NIH HHS K23 AI104315NIAID NIH HHS U01 AI084735NIAID NIH HHS U01 AI84735
6 · The paper itself

Abstract

backgroundElevated immune activation is associated with an increased risk of HIV acquisition. Tenofovir (TFV) has immunomodulatory properties in vitro, but how this extends in vivo remains unknown.

methodsHIV-negative adults received daily coformulated TFV disoproxil fumarate 300 mg/emtricitabine (FTC) 200 mg for 30 days followed by a 30-day washout. Markers of T-cell activation, inflammation, and cytokines were measured before drug and on days 30 (on drug) and 60 (30-day washout). Data were analyzed using one-way analysis of variance/pairwise comparisons. Intracellular disposition of TFV-diphosphate and FTC-triphosphate in CD4 and CD8 T-cells and monocytes was characterized, and the relationship with immune activation was evaluated using Pearson's correlation coefficient.

resultsT-cell activation was available in 19 participants. CD38/HLA-DR coexpression on CD8 T-cells decreased from baseline to day 30 (3.97% vs. 2.71%; P = 0.03) and day 60 (3.97% vs. 2.41%; P = 0.008). Soluble CD27 decreased from baseline to day 60 (184.1 vs. 168.4 pg/mL; P = 0.001). Cytokines and inflammation markers were not significantly different. TFV-diphosphate and FTC-triphosphate were approximately 4-fold higher in monocytes vs. CD4 and CD8 T-cells but neither correlated with activation markers.

conclusionsTFV disoproxil fumarate/FTC therapy was associated with decreased T-cell activation in HIV-negative adults, which could contribute to the antiviral effect of pre-exposure prophylaxis (NCT01040091; www.clinicaltrials.gov).

Indexed as

AdenineAdolescentAdultAnti-HIV AgentsDeoxycytidineEmtricitabineFemaleHumansImmunologic FactorsLymphocyte ActivationMaleMiddle AgedOrganophosphonatesPre-Exposure ProphylaxisTenofovirYoung AdultAdenineAnti-HIV AgentsDeoxycytidineEmtricitabineImmunologic FactorsOrganophosphonatesTenofovir

Identifiers

PMID25763783
PMCPMC4358752
OpenAlexW1990567474

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.