Evidence map›Paper›PMID 29746648›Full record

Trial reportThe Journal of antimicrobial chemotherapy2018

Effects of sofosbuvir-based hepatitis C treatment on the pharmacokinetics of tenofovir in HIV/HCV-coinfected individuals receiving tenofovir disoproxil fumarate.

Christine E MacBrayne, Kristen M Marks, Daniel S Fierer, Susanna Naggie, Raymond T Chung, Michael D Hughes, Arthur Y Kim, Marion G Peters, Diana M Brainard, Sharon M Seifert and 4 more

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in The Journal of antimicrobial chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

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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

14 authors at 8 institutions in 1 country.

Christine E MacBrayneUniversity of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
Kristen M MarksNew York Presbyterian Hospital, New York, NY, USA.
Daniel S FiererIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Susanna NaggieDuke Clinical Research Institute, Durham, NC, USA.
Raymond T ChungMassachusetts General Hospital, Boston, MA, USA.
Michael D HughesHarvard T. H. Chan School of Public Health, Boston, MA, USA.
Arthur Y KimMassachusetts General Hospital, Boston, MA, USA.
Marion G PetersUniversity of California, San Francisco, CA, USA.
Diana M BrainardGilead Sciences, Foster City, CA, USA.
Sharon M SeifertUniversity of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
Jose R Castillo-MancillaUniversity of Colorado Department of Medicine, Aurora, CO, USA.
Lane R BushmanUniversity of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
Peter L AndersonUniversity of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
Jennifer J KiserUniversity of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
Massachusetts General Hospital · USClinical Research Institute · USGilead Sciences (United States) · USHarvard University · USIcahn School of Medicine at Mount Sinai · USNewYork–Presbyterian Hospital · USUniversity of California, San Francisco · USUniversity of Colorado Denver · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
Statistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010
$71.9M
Harvard Medical School Vaccine Clinical Trials UnitUM1AI069412 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Lindsey Robert Baden, Daniel R. Kuritzkes · 2012 to 2026
$57.2M
UCSD Department of Medicine HIV/AIDS Clinical Trials UnitUM1AI069432 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TIMOTHY J. WILKIN · 2012 to 2026
$50.4M
Clinical and Translational Science CenterUL1TR000457 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 2012 to 2016
$46.0M
Weill Cornell Medicine - Rutgers New Jersey Medical School Clinical Trials UnitUM1AI069419 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI ROY M. GULICK · 2012 to 2026
$44.6M
Terry Beirn CPCRA Clinical Trials UnitUM1AI069503 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI KAN, VIRGINIA · 2012 to 2020
$38.5M
The Johns Hopkins Baltimore-Washington-India Clinical Trials Unit (BWI CTU)UM1AI069465 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Charles W. Flexner, Amita Gupta · 2012 to 2026
$34.1M
University of Pennsylvania HIV Clinical Trials UnitUM1AI069534 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ian Frank, PABLO TEBAS · 2012 to 2026
$33.0M
NCATS NIH HHS UL1 TR000457NIAID NIH HHS P30 AI045008NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI069419NIAID NIH HHS U01 AI069432NIAID NIH HHS U01 AI069471NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069412NIAID NIH HHS UM1 AI069419NIAID NIH HHS UM1 AI069432NIAID NIH HHS UM1 AI069465NIAID NIH HHS UM1 AI069471NIAID NIH HHS UM1 AI069496NIAID NIH HHS UM1 AI069503NIAID NIH HHS UM1 AI069534NIAID NIH HHS UM1 AI106701NIDA NIH HHS R01 DA040499
6 · The paper itself

Abstract

Background: The nucleotide analogues tenofovir and sofosbuvir are considered to have low potential for drug interactions. Objectives: To determine the effect of sofosbuvir-based HCV treatment on plasma concentrations of tenofovir and cellular concentrations of tenofovir diphosphate. Methods: HIV-infected participants with acute HCV were treated for 12 weeks with sofosbuvir + ribavirin in Cohort 1 or 8 weeks with ledipasvir/sofosbuvir in Cohort 2 of AIDS Clinical Trials Group study 5327. Only participants taking tenofovir disoproxil fumarate were included in this analysis. Tenofovir in plasma, tenofovir diphosphate in dried blood spots and tenofovir diphosphate in PBMCs were measured pre-HCV therapy and longitudinally during the study using validated LC/MS-MS. Results: Fifteen and 22 men completed Cohorts 1 and 2, respectively. In Cohort 1, tenofovir diphosphate was 4.3-fold higher (95% CI geometric mean ratio 2.46-7.67; P = 0.0001) in dried blood spots and 2.3-fold higher (95% CI 1.09-4.92; P = 0.03) in PBMCs following 12 weeks of sofosbuvir + ribavirin versus study entry. Tenofovir in the plasma was unchanged. In Cohort 2, tenofovir diphosphate was 17.8-fold higher (95% CI 12.77-24.86; P < 0.0001) in dried blood spots after 8 weeks of ledipasvir/sofosbuvir versus study entry. Tenofovir plasma concentrations were 2.1-fold higher (95% CI 1.44-2.91; P = 0.0005). Despite the increase in cellular tenofovir diphosphate concentrations, only a small decline in CLCR (6%-7%) was observed in both cohorts between study entry and end of treatment. Conclusions: These data indicate an unexpected drug interaction with tenofovir disoproxil fumarate and sofosbuvir at the cellular level. Additional studies are needed to determine the mechanism and clinical significance.

Indexed as

AdenineAdultAntiviral AgentsBenzimidazolesCoinfectionDrug InteractionsFluorenesHepatitis CHIV InfectionsHumansMaleMiddle AgedOrganophosphatesRibavirinSofosbuvirTenofovirAdenineAntiviral AgentsBenzimidazolesFluorenesledipasvir, sofosbuvir drug combinationOrganophosphatesRibavirinSofosbuvirTenofovirtenofovir diphosphateUridine Monophosphate

Identifiers

PMID29746648
PMCPMC6054189
OpenAlexW2799598885

What OpenQuestion holds

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Registered trials

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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.