Evidence map›Paper›PMID 29334548›Full record

ArticleAIDS (London, England)2018

Plasma and intracellular pharmacokinetics of tenofovir in patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide.

Anthony T Podany, Sara H Bares, Joshua Havens, Shetty Ravi Dyavar, Jennifer O'Neill, Sarah Lee, Courtney V Fletcher, Susan Swindells, Kimberly K Scarsi

Abstract readClinical Study
In one paragraph

Article in AIDS (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
–field-weighted citation impact
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

52 citing papers in PubMed.

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  3. Lipid and Glucose Profiles in Pregnant Women With HIV on Tenofovir-based Antiretroviral Therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Anthony T PodanyAntiviral Pharmacology Laboratory, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC).
Sara H BaresDivision of Infectious Diseases, Department of Internal Medicine, College of Medicine (COM), UNMC.
Joshua HavensDivision of Infectious Diseases, Department of Internal Medicine, College of Medicine (COM), UNMC.
Shetty Ravi DyavarAntiviral Pharmacology Laboratory, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC).
Jennifer O'NeillDivision of Infectious Diseases, Department of Internal Medicine, College of Medicine (COM), UNMC.
Sarah LeeCOM, UNMC, Omaha, Nebraska, USA.
Courtney V FletcherAntiviral Pharmacology Laboratory, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC).
Susan SwindellsDivision of Infectious Diseases, Department of Internal Medicine, College of Medicine (COM), UNMC.
Kimberly K ScarsiAntiviral Pharmacology Laboratory, College of Pharmacy (COP), University of Nebraska Medical Center (UNMC).

Funding

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
Tracking and Evaluation CoreU54GM115458 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI RIZZO, MATTHEW · 2016 to 2025
$42.8M
The Lymphoid Tissue Pharmacology of Antiretroviral DrugsR01AI124965 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI FLETCHER, COURTNEY V · 2016 to 2020
$3.7M
Pharmacological Strategies to use the Levonorgestrel Implant in HIV-infected WomenR01HD085887 · NICHD · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SCARSI, KIMBERLY K. · 2015 to 2020
$1.4M
Clinical Pharmacology of Efavirenz Combined with High Dose RifapentineK23AI134307 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PODANY, ANTHONY T · 2018 to 2022
$819k
NIAID NIH HHS K23 AI134307NIAID NIH HHS R01 AI124965NIAID NIH HHS UM1 AI106701NICHD NIH HHS R01 HD085887NIGMS NIH HHS U54 GM115458
6 · The paper itself

Abstract

objectivesThe aim of the study was to compare the intraindividual plasma and intracellular peripheral blood mononuclear cell (PBMC) pharmacokinetics of tenofovir (TFV) and its intracellular metabolite, TFV-diphosphate (TFV-DP) in patients switched from a fixed-dose combination (FDC) tablet of TFV disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir (EVG)/cobicistat (COBI) to a FDC containing TFV alafenamide (TAF)/FTC/EVG/COBI.

designA single-arm, prospective, nonrandomized, cross-over, pharmacokinetic study in patients receiving a TDF-containing regimen (TDF 300 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg) switched to a TAF-containing FDC regimen (TAF 10 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg).

methodsSingle, sparse plasma and PBMC samples were collected during TDF therapy and 4-8 weeks post-switch to the TAF-containing regimen. Plasma TFV and cell associated TFV-DP concentrations were determined with validated liquid chromatography tandem mass spectrometry methods. PBMC cell enumeration was performed by quantification of RNaseP (RPP30) gene copy numbers using a highly sensitive droplet digital PCR assay. Plasma and PBMC pharmacokinetics were summarized as geometric mean and compared as a geometric mean ratio with a Wilcoxon signed-rank test.

resultsIn 30 participants with evaluable data, TFV plasma concentrations decreased 90% [TDF: 99.98 (2.24) ng/ml vs. TAF: 10.2 (1.6) ng/ml, P < 0.001] after the switch while cell-associated TFV-DP increased 2.41-fold [TAF: 834.7 (2.49) vs. TDF: 346.85 (3.75) fmol/10 cells, P = 0.004].

conclusionIntraindividually, plasma TFV concentrations significantly decreased while cell associated TFV-DP concentrations significantly increased after switching from a TDF to a TAF-containing antiretroviral therapy regimen.

Indexed as

Drug SubstitutionAdenineAdultAgedAged, 80 and overAlanineAnti-HIV AgentsChromatography, LiquidCross-Over StudiesFemaleHIV InfectionsHumansLeukocytes, MononuclearMaleMiddle AgedPlasmaAdenineAlanineAnti-HIV AgentsTenofovirtenofovir alafenamide

Identifiers

PMID29334548
PMCPMC5854526

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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.