Evidence map›Paper›PMID 23600365›Full record

Trial reportAIDS research and human retroviruses2013

Single dose pharmacokinetics of oral tenofovir in plasma, peripheral blood mononuclear cells, colonic tissue, and vaginal tissue.

Nicolette A Louissaint, Ying-Jun Cao, Paul L Skipper, Rosa G Liberman, Steven R Tannenbaum, Sridhar Nimmagadda, Jean R Anderson, Stephanie Everts, Rahul Bakshi, Edward J Fuchs and 1 more

Open access · greenAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in AIDS research and human retroviruses, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed, 1 pooled it
10.6field-weighted citation impact, top 1% 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

108 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.

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  14. Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT.Journal of acquired immune deficiency syndromes (1999) · 2017
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48 more citing papers are in PubMed but not listed here.

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

11 authors at 2 institutions in 1 country.

Nicolette A Louissaint1 Johns Hopkins University , Baltimore, Maryland.
Ying-Jun Cao
Paul L Skipper
Rosa G Liberman
Steven R Tannenbaum
Sridhar Nimmagadda
Jean R Anderson
Stephanie Everts
Rahul Bakshi
Edward J Fuchs
Craig W Hendrix
Johns Hopkins University · USMassachusetts Institute of Technology · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
NCRR NIH HHS UL1 RR 025005
6 · The paper itself

Abstract

HIV seroconversion outcomes in preexposure prophylaxis (PrEP) trials of oral tenofovir (TFV)-containing regimens are highly sensitive to drug concentration, yet less-than-daily dosing regimens are under study. Description of TFV and its active moiety, TFV diphosphate (TFV-DP), in blood, vaginal tissue, and colon tissue may guide the design and interpretation of PrEP clinical trials. Six healthy women were administered a single oral dose of 300 mg tenofovir disoproxil fumarate (TDF) and 4.3 mg (12.31 MBq, 333 μCi) (14)C-TDF slurry. Blood was collected every 4 h for the first 24 h, then at 4, 8, 11, and 15 days postdosing. Colonic and vaginal samples (tissue, total and CD4(+) cells, luminal fluid and cells) were collected 1, 8 and 15 days postdose. Samples were analyzed for TFV and TFV-DP. Plasma TFV demonstrated triphasic decay with terminal elimination half-life median [interquartile range (IQR)] 69 h (58-77). Peripheral blood mononuclear cell (PBMC) TFV-DP demonstrated biphasic peaks (median 12 h and 96 h) followed by a terminal 48 h (38-76) half-life; Cmax was 20 fmol/million cells (2-63). One day postdose, the TFV-DP paired colon:vaginal tissue concentration ratio was 1 or greater in all subjects' tissue homogenates, median 124 (range 1-281), but was not sustained. The ratio was lower and more variable in cells extracted from tissue. Among all sample types, TFV and TFV-DP half-life ranged from 23 to 139 h. PBMC TFV-DP rose slowly in the hours after dosing indicating that success with exposure-driven dosing regimens may be sensitive to timing of the dose prior to exposure. Colonic tissue homogenate TFV-DP concentrations were greater than in vaginal homogenate at 24 h, but not in cells extracted from tissue. These and the other pharmacokinetic findings will guide the interpretation and design of future PrEP trials.

Indexed as

AdenineAdministration, OralAdultAnti-HIV AgentsCarbon RadioisotopesColonFemaleHumansIsotope LabelingLeukocytes, MononuclearOrganophosphonatesPlasmaTenofovirVaginaAdenineAnti-HIV AgentsCarbon RadioisotopesOrganophosphonatesTenofovir

Identifiers

PMID23600365
PMCPMC3809387
OpenAlexW2075290265

What OpenQuestion holds

Textmetadata
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.