Correlation between Compartmental Tenofovir Concentrations and an Ex Vivo Rectal Biopsy Model of Tissue Infectibility in the RMP-02/MTN-006 Phase 1 Study
Identifieur interne : 003C10 ( Ncbi/Merge ); précédent : 003C09; suivant : 003C11Correlation between Compartmental Tenofovir Concentrations and an Ex Vivo Rectal Biopsy Model of Tissue Infectibility in the RMP-02/MTN-006 Phase 1 Study
Auteurs : Nicola Richardson-Harman [États-Unis] ; Craig W. Hendrix [États-Unis] ; Namandjé N. Bumpus [États-Unis] ; Christine Mauck [États-Unis] ; Ross D. Cranston [États-Unis] ; Kuo Yang [États-Unis] ; Julie Elliott [États-Unis] ; Karen Tanner [États-Unis] ; Ian Mcgowan [États-Unis] ; Angela Kashuba [États-Unis] ; Peter A. Anton [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
Descripteurs français
- KwdFr :
- Administration par voie orale, Administration par voie rectale, Adulte, Biopsie, Cellulose (), Cellulose (analogues et dérivés), Crèmes, mousses et gels vaginaux (), Femelle, Gels, Humains, Infections à VIH (), Jeune adulte, Mâle, Méthode en double aveugle, Rectum (), Relation dose-effet des médicaments, Ténofovir (administration et posologie), Ténofovir (pharmacocinétique).
- MESH :
- administration et posologie : Ténofovir.
- analogues et dérivés : Cellulose.
- pharmacocinétique : Ténofovir.
- Administration par voie orale, Administration par voie rectale, Adulte, Biopsie, Cellulose, Crèmes, mousses et gels vaginaux, Femelle, Gels, Humains, Infections à VIH, Jeune adulte, Mâle, Méthode en double aveugle, Rectum, Relation dose-effet des médicaments.
English descriptors
- KwdEn :
- Administration, Oral, Administration, Rectal, Adult, Biopsy, Cellulose (analogs & derivatives), Cellulose (chemistry), Dose-Response Relationship, Drug, Double-Blind Method, Female, Gels, HIV Infections (prevention & control), Humans, Male, Rectum (drug effects), Tenofovir (administration & dosage), Tenofovir (pharmacokinetics), Vaginal Creams, Foams, and Jellies (chemistry), Young Adult.
- MESH :
- chemical , administration & dosage : Tenofovir.
- chemical , analogs & derivatives : Cellulose.
- chemical , chemistry : Cellulose, Vaginal Creams, Foams, and Jellies.
- drug effects : Rectum.
- chemical , pharmacokinetics : Tenofovir.
- prevention & control : HIV Infections.
- Administration, Oral, Administration, Rectal, Adult, Biopsy, Dose-Response Relationship, Drug, Double-Blind Method, Female, Gels, Humans, Male, Young Adult.
Abstract
This study was designed to assess the dose-response relationship between tissue, blood, vaginal and rectal compartment concentrations of tenofovir (TFV) and tenofovir diphosphate (TFVdp) and
Phase 1, randomized, two-site (US), double-blind, placebo-controlled study of sexually-abstinent males and females.
Eighteen participants received a single 300 mg exposure of oral TDF and were then randomized 2∶1 to receive a single then seven-daily rectal exposures of TFV 1% gel (40 mg TFV per 4 ml gel application) or hydroxyethyl-cellulose (HEC) placebo gel. Blood and rectal biopsies were collected for pharmacokinetic TDF and TFVdp analyses and
There was a significant fit for the TFVdp dose-response model for rectal tissue (
The TFVdp MMC compartment (CD4+, CD4− and Total) provided the best surrogate for biopsy infectibility and the 7-daily topical TFV gel treatment provided the strongest PK profile for HIV suppression.
ClinicalTrials.gov
Url:
DOI: 10.1371/journal.pone.0111507
PubMed: 25350130
PubMed Central: 4211741
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 001D87
- to stream Pmc, to step Curation: 001D62
- to stream Pmc, to step Checkpoint: 001769
- to stream PubMed, to step Corpus: 001807
- to stream PubMed, to step Curation: 001800
- to stream PubMed, to step Checkpoint: 001800
Links to Exploration step
PMC:4211741Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Correlation between Compartmental Tenofovir Concentrations and an <italic>Ex Vivo</italic>
Rectal Biopsy Model of Tissue Infectibility in the RMP-02/MTN-006 Phase 1 Study</title>
<author><name sortKey="Richardson Harman, Nicola" sort="Richardson Harman, Nicola" uniqKey="Richardson Harman N" first="Nicola" last="Richardson-Harman">Nicola Richardson-Harman</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Alpha StatConsult, LLC, Damascus, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Alpha StatConsult, LLC, Damascus, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hendrix, Craig W" sort="Hendrix, Craig W" uniqKey="Hendrix C" first="Craig W." last="Hendrix">Craig W. Hendrix</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bumpus, Namandje N" sort="Bumpus, Namandje N" uniqKey="Bumpus N" first="Namandjé N." last="Bumpus">Namandjé N. Bumpus</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mauck, Christine" sort="Mauck, Christine" uniqKey="Mauck C" first="Christine" last="Mauck">Christine Mauck</name>
<affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>CONRAD, Arlington, VA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>CONRAD, Arlington, VA</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cranston, Ross D" sort="Cranston, Ross D" uniqKey="Cranston R" first="Ross D." last="Cranston">Ross D. Cranston</name>
<affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Yang, Kuo" sort="Yang, Kuo" uniqKey="Yang K" first="Kuo" last="Yang">Kuo Yang</name>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Elliott, Julie" sort="Elliott, Julie" uniqKey="Elliott J" first="Julie" last="Elliott">Julie Elliott</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tanner, Karen" sort="Tanner, Karen" uniqKey="Tanner K" first="Karen" last="Tanner">Karen Tanner</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgowan, Ian" sort="Mcgowan, Ian" uniqKey="Mcgowan I" first="Ian" last="Mcgowan">Ian Mcgowan</name>
<affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kashuba, Angela" sort="Kashuba, Angela" uniqKey="Kashuba A" first="Angela" last="Kashuba">Angela Kashuba</name>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Anton, Peter A" sort="Anton, Peter A" uniqKey="Anton P" first="Peter A." last="Anton">Peter A. Anton</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25350130</idno>
<idno type="pmc">4211741</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211741</idno>
<idno type="RBID">PMC:4211741</idno>
<idno type="doi">10.1371/journal.pone.0111507</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">001D87</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D87</idno>
<idno type="wicri:Area/Pmc/Curation">001D62</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001D62</idno>
<idno type="wicri:Area/Pmc/Checkpoint">001769</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001769</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">001807</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001807</idno>
<idno type="wicri:Area/PubMed/Curation">001800</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001800</idno>
<idno type="wicri:Area/PubMed/Checkpoint">001800</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001800</idno>
<idno type="wicri:Area/Ncbi/Merge">003C10</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Correlation between Compartmental Tenofovir Concentrations and an <italic>Ex Vivo</italic>
Rectal Biopsy Model of Tissue Infectibility in the RMP-02/MTN-006 Phase 1 Study</title>
<author><name sortKey="Richardson Harman, Nicola" sort="Richardson Harman, Nicola" uniqKey="Richardson Harman N" first="Nicola" last="Richardson-Harman">Nicola Richardson-Harman</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Alpha StatConsult, LLC, Damascus, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Alpha StatConsult, LLC, Damascus, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hendrix, Craig W" sort="Hendrix, Craig W" uniqKey="Hendrix C" first="Craig W." last="Hendrix">Craig W. Hendrix</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bumpus, Namandje N" sort="Bumpus, Namandje N" uniqKey="Bumpus N" first="Namandjé N." last="Bumpus">Namandjé N. Bumpus</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mauck, Christine" sort="Mauck, Christine" uniqKey="Mauck C" first="Christine" last="Mauck">Christine Mauck</name>
<affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>CONRAD, Arlington, VA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>CONRAD, Arlington, VA</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cranston, Ross D" sort="Cranston, Ross D" uniqKey="Cranston R" first="Ross D." last="Cranston">Ross D. Cranston</name>
<affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Yang, Kuo" sort="Yang, Kuo" uniqKey="Yang K" first="Kuo" last="Yang">Kuo Yang</name>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Elliott, Julie" sort="Elliott, Julie" uniqKey="Elliott J" first="Julie" last="Elliott">Julie Elliott</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tanner, Karen" sort="Tanner, Karen" uniqKey="Tanner K" first="Karen" last="Tanner">Karen Tanner</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgowan, Ian" sort="Mcgowan, Ian" uniqKey="Mcgowan I" first="Ian" last="Mcgowan">Ian Mcgowan</name>
<affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kashuba, Angela" sort="Kashuba, Angela" uniqKey="Kashuba A" first="Angela" last="Kashuba">Angela Kashuba</name>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Anton, Peter A" sort="Anton, Peter A" uniqKey="Anton P" first="Peter A." last="Anton">Peter A. Anton</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Oral</term>
<term>Administration, Rectal</term>
<term>Adult</term>
<term>Biopsy</term>
<term>Cellulose (analogs & derivatives)</term>
<term>Cellulose (chemistry)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Gels</term>
<term>HIV Infections (prevention & control)</term>
<term>Humans</term>
<term>Male</term>
<term>Rectum (drug effects)</term>
<term>Tenofovir (administration & dosage)</term>
<term>Tenofovir (pharmacokinetics)</term>
<term>Vaginal Creams, Foams, and Jellies (chemistry)</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Administration par voie orale</term>
<term>Administration par voie rectale</term>
<term>Adulte</term>
<term>Biopsie</term>
<term>Cellulose ()</term>
<term>Cellulose (analogues et dérivés)</term>
<term>Crèmes, mousses et gels vaginaux ()</term>
<term>Femelle</term>
<term>Gels</term>
<term>Humains</term>
<term>Infections à VIH ()</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Méthode en double aveugle</term>
<term>Rectum ()</term>
<term>Relation dose-effet des médicaments</term>
<term>Ténofovir (administration et posologie)</term>
<term>Ténofovir (pharmacocinétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Tenofovir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Cellulose</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cellulose</term>
<term>Vaginal Creams, Foams, and Jellies</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Ténofovir</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Cellulose</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Rectum</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Ténofovir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Tenofovir</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>HIV Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Administration, Oral</term>
<term>Administration, Rectal</term>
<term>Adult</term>
<term>Biopsy</term>
<term>Dose-Response Relationship, Drug</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Gels</term>
<term>Humans</term>
<term>Male</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Administration par voie orale</term>
<term>Administration par voie rectale</term>
<term>Adulte</term>
<term>Biopsie</term>
<term>Cellulose</term>
<term>Crèmes, mousses et gels vaginaux</term>
<term>Femelle</term>
<term>Gels</term>
<term>Humains</term>
<term>Infections à VIH</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Méthode en double aveugle</term>
<term>Rectum</term>
<term>Relation dose-effet des médicaments</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Objectives</title>
<p>This study was designed to assess the dose-response relationship between tissue, blood, vaginal and rectal compartment concentrations of tenofovir (TFV) and tenofovir diphosphate (TFVdp) and <italic>ex vivo</italic>
rectal HIV suppression following oral tenofovir disoproxil fumarate (TDF) and rectal administration of TFV 1% vaginally-formulated gel.</p>
</sec>
<sec><title>Design</title>
<p>Phase 1, randomized, two-site (US), double-blind, placebo-controlled study of sexually-abstinent males and females.</p>
</sec>
<sec><title>Methods</title>
<p>Eighteen participants received a single 300 mg exposure of oral TDF and were then randomized 2∶1 to receive a single then seven-daily rectal exposures of TFV 1% gel (40 mg TFV per 4 ml gel application) or hydroxyethyl-cellulose (HEC) placebo gel. Blood and rectal biopsies were collected for pharmacokinetic TDF and TFVdp analyses and <italic>ex vivo</italic>
HIV-1 challenge.</p>
</sec>
<sec><title>Results</title>
<p>There was a significant fit for the TFVdp dose-response model for rectal tissue (<italic>p</italic>
= 0.0004), CD4<sup>+</sup>
<sub>MMC</sub>
(<italic>p</italic>
<0.0001), CD4<sup>−</sup>
<sub>MMC</sub>
(<italic>p</italic>
<0.0001), and Total<sub>MMC</sub>
(<italic>p</italic>
<0.0001) compartments with <italic>r<sup>2</sup>
</italic>
ranging 0.36–0.64. Higher concentrations of TFVdp corresponded with lower p24, consistent with drug-mediated virus suppression. The single oral treatment failed to provide adequate compartment drug exposure to reach the EC<sub>50</sub>
of rectal tissue TFVdp predicted to be necessary to suppress HIV in rectal tissue. The EC<sub>50</sub>
for CD4<sup>+</sup>
<sub>MMC</sub>
was within the single topical treatment range, providing evidence that a 1% topical, vaginally-formulated TFV gel provided <italic>in-vivo</italic>
doses predicted to provide for 50% efficacy in the <italic>ex vivo</italic>
assay. The 7-daily topical TFV gel treatment provided TFVdp concentrations that reached EC<sub>90</sub>
biopsy efficacy for CD4<sup>−</sup>
<sub>MMC</sub>
, CD4<sup>+</sup>
<sub>MMC</sub>
and Total<sub>MMC</sub>
compartments.</p>
</sec>
<sec><title>Conclusion</title>
<p>The TFVdp MMC compartment (CD4+, CD4− and Total) provided the best surrogate for biopsy infectibility and the 7-daily topical TFV gel treatment provided the strongest PK profile for HIV suppression.</p>
</sec>
<sec><title></title>
<p>ClinicalTrials.gov <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov/ct2/show/NCT00984971">NCT00984971.</ext-link>
</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abner, Sr" uniqKey="Abner S">SR Abner</name>
</author>
<author><name sortKey="Guenthner, Pc" uniqKey="Guenthner P">PC Guenthner</name>
</author>
<author><name sortKey="Guarner, J" uniqKey="Guarner J">J Guarner</name>
</author>
<author><name sortKey="Hancock, Ka" uniqKey="Hancock K">KA Hancock</name>
</author>
<author><name sortKey="Cummins, Je" uniqKey="Cummins J">JE Cummins</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Batman, Pa" uniqKey="Batman P">PA Batman</name>
</author>
<author><name sortKey="Fleming, Sc" uniqKey="Fleming S">SC Fleming</name>
</author>
<author><name sortKey="Sedgwick, Pm" uniqKey="Sedgwick P">PM Sedgwick</name>
</author>
<author><name sortKey="Macdonald, Tt" uniqKey="Macdonald T">TT MacDonald</name>
</author>
<author><name sortKey="Griffin, Ge" uniqKey="Griffin G">GE Griffin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fischetti, L" uniqKey="Fischetti L">L Fischetti</name>
</author>
<author><name sortKey="Barry, Sm" uniqKey="Barry S">SM Barry</name>
</author>
<author><name sortKey="Hope, Tj" uniqKey="Hope T">TJ Hope</name>
</author>
<author><name sortKey="Shattock, Rj" uniqKey="Shattock R">RJ Shattock</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Greenhead, P" uniqKey="Greenhead P">P Greenhead</name>
</author>
<author><name sortKey="Hayes, P" uniqKey="Hayes P">P Hayes</name>
</author>
<author><name sortKey="Watts, Ps" uniqKey="Watts P">PS Watts</name>
</author>
<author><name sortKey="Laing, Kg" uniqKey="Laing K">KG Laing</name>
</author>
<author><name sortKey="Griffin, Ge" uniqKey="Griffin G">GE Griffin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hladik, F" uniqKey="Hladik F">F Hladik</name>
</author>
<author><name sortKey="Doncel, Gf" uniqKey="Doncel G">GF Doncel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anton, Pa" uniqKey="Anton P">PA Anton</name>
</author>
<author><name sortKey="Cranston, Rd" uniqKey="Cranston R">RD Cranston</name>
</author>
<author><name sortKey="Kashuba, A" uniqKey="Kashuba A">A Kashuba</name>
</author>
<author><name sortKey="Hendrix, Cw" uniqKey="Hendrix C">CW Hendrix</name>
</author>
<author><name sortKey="Bumpus, Nn" uniqKey="Bumpus N">NN Bumpus</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anton, Pa" uniqKey="Anton P">PA Anton</name>
</author>
<author><name sortKey="Saunders, T" uniqKey="Saunders T">T Saunders</name>
</author>
<author><name sortKey="Elliott, J" uniqKey="Elliott J">J Elliott</name>
</author>
<author><name sortKey="Khanukhova, E" uniqKey="Khanukhova E">E Khanukhova</name>
</author>
<author><name sortKey="Dennis, R" uniqKey="Dennis R">R Dennis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Richardson Harman, N" uniqKey="Richardson Harman N">N Richardson-Harman</name>
</author>
<author><name sortKey="Mauck, C" uniqKey="Mauck C">C Mauck</name>
</author>
<author><name sortKey="Mcgowan, I" uniqKey="Mcgowan I">I McGowan</name>
</author>
<author><name sortKey="Anton, P" uniqKey="Anton P">P Anton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tien, D" uniqKey="Tien D">D Tien</name>
</author>
<author><name sortKey="Schnaare, Rl" uniqKey="Schnaare R">RL Schnaare</name>
</author>
<author><name sortKey="Kang, F" uniqKey="Kang F">F Kang</name>
</author>
<author><name sortKey="Cohl, G" uniqKey="Cohl G">G Cohl</name>
</author>
<author><name sortKey="Mccormick, Tj" uniqKey="Mccormick T">TJ McCormick</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hendrix, Cw" uniqKey="Hendrix C">CW Hendrix</name>
</author>
<author><name sortKey="Chen, Ba" uniqKey="Chen B">BA Chen</name>
</author>
<author><name sortKey="Guddera, V" uniqKey="Guddera V">V Guddera</name>
</author>
<author><name sortKey="Hoesley, C" uniqKey="Hoesley C">C Hoesley</name>
</author>
<author><name sortKey="Justman, J" uniqKey="Justman J">J Justman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anton, Pa" uniqKey="Anton P">PA Anton</name>
</author>
<author><name sortKey="Elliott, J" uniqKey="Elliott J">J Elliott</name>
</author>
<author><name sortKey="Poles, Ma" uniqKey="Poles M">MA Poles</name>
</author>
<author><name sortKey="Mcgowan, Im" uniqKey="Mcgowan I">IM McGowan</name>
</author>
<author><name sortKey="Matud, J" uniqKey="Matud J">J Matud</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fletcher, Ps" uniqKey="Fletcher P">PS Fletcher</name>
</author>
<author><name sortKey="Elliott, J" uniqKey="Elliott J">J Elliott</name>
</author>
<author><name sortKey="Grivel, Jc" uniqKey="Grivel J">JC Grivel</name>
</author>
<author><name sortKey="Margolis, L" uniqKey="Margolis L">L Margolis</name>
</author>
<author><name sortKey="Anton, P" uniqKey="Anton P">P Anton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Richardson Harman, N" uniqKey="Richardson Harman N">N Richardson-Harman</name>
</author>
<author><name sortKey="Lackman Smith, C" uniqKey="Lackman Smith C">C Lackman-Smith</name>
</author>
<author><name sortKey="Fletcher, Ps" uniqKey="Fletcher P">PS Fletcher</name>
</author>
<author><name sortKey="Anton, Pa" uniqKey="Anton P">PA Anton</name>
</author>
<author><name sortKey="Bremer, Jw" uniqKey="Bremer J">JW Bremer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Glatting, G" uniqKey="Glatting G">G Glatting</name>
</author>
<author><name sortKey="Kletting, P" uniqKey="Kletting P">P Kletting</name>
</author>
<author><name sortKey="Reske, Sn" uniqKey="Reske S">SN Reske</name>
</author>
<author><name sortKey="Hohl, K" uniqKey="Hohl K">K Hohl</name>
</author>
<author><name sortKey="Ring, C" uniqKey="Ring C">C Ring</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yang, K H" uniqKey="Yang K">K-H Yang</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Tebit, Dm" uniqKey="Tebit D">DM Tebit</name>
</author>
<author><name sortKey="Ndembi, N" uniqKey="Ndembi N">N Ndembi</name>
</author>
<author><name sortKey="Weinberg, A" uniqKey="Weinberg A">A Weinberg</name>
</author>
<author><name sortKey="Quinones Mateu, Me" uniqKey="Quinones Mateu M">ME Quinones-Mateu</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<double pmid="25350130"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Correlation between Compartmental Tenofovir Concentrations and an <italic>Ex Vivo</italic>
Rectal Biopsy Model of Tissue Infectibility in the RMP-02/MTN-006 Phase 1 Study</title>
<author><name sortKey="Richardson Harman, Nicola" sort="Richardson Harman, Nicola" uniqKey="Richardson Harman N" first="Nicola" last="Richardson-Harman">Nicola Richardson-Harman</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Alpha StatConsult, LLC, Damascus, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Alpha StatConsult, LLC, Damascus, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hendrix, Craig W" sort="Hendrix, Craig W" uniqKey="Hendrix C" first="Craig W." last="Hendrix">Craig W. Hendrix</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bumpus, Namandje N" sort="Bumpus, Namandje N" uniqKey="Bumpus N" first="Namandjé N." last="Bumpus">Namandjé N. Bumpus</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mauck, Christine" sort="Mauck, Christine" uniqKey="Mauck C" first="Christine" last="Mauck">Christine Mauck</name>
<affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>CONRAD, Arlington, VA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>CONRAD, Arlington, VA</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cranston, Ross D" sort="Cranston, Ross D" uniqKey="Cranston R" first="Ross D." last="Cranston">Ross D. Cranston</name>
<affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Yang, Kuo" sort="Yang, Kuo" uniqKey="Yang K" first="Kuo" last="Yang">Kuo Yang</name>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Elliott, Julie" sort="Elliott, Julie" uniqKey="Elliott J" first="Julie" last="Elliott">Julie Elliott</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tanner, Karen" sort="Tanner, Karen" uniqKey="Tanner K" first="Karen" last="Tanner">Karen Tanner</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgowan, Ian" sort="Mcgowan, Ian" uniqKey="Mcgowan I" first="Ian" last="Mcgowan">Ian Mcgowan</name>
<affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kashuba, Angela" sort="Kashuba, Angela" uniqKey="Kashuba A" first="Angela" last="Kashuba">Angela Kashuba</name>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Anton, Peter A" sort="Anton, Peter A" uniqKey="Anton P" first="Peter A." last="Anton">Peter A. Anton</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25350130</idno>
<idno type="pmc">4211741</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211741</idno>
<idno type="RBID">PMC:4211741</idno>
<idno type="doi">10.1371/journal.pone.0111507</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">001D87</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D87</idno>
<idno type="wicri:Area/Pmc/Curation">001D62</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001D62</idno>
<idno type="wicri:Area/Pmc/Checkpoint">001769</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001769</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Correlation between Compartmental Tenofovir Concentrations and an <italic>Ex Vivo</italic>
Rectal Biopsy Model of Tissue Infectibility in the RMP-02/MTN-006 Phase 1 Study</title>
<author><name sortKey="Richardson Harman, Nicola" sort="Richardson Harman, Nicola" uniqKey="Richardson Harman N" first="Nicola" last="Richardson-Harman">Nicola Richardson-Harman</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Alpha StatConsult, LLC, Damascus, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Alpha StatConsult, LLC, Damascus, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hendrix, Craig W" sort="Hendrix, Craig W" uniqKey="Hendrix C" first="Craig W." last="Hendrix">Craig W. Hendrix</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bumpus, Namandje N" sort="Bumpus, Namandje N" uniqKey="Bumpus N" first="Namandjé N." last="Bumpus">Namandjé N. Bumpus</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mauck, Christine" sort="Mauck, Christine" uniqKey="Mauck C" first="Christine" last="Mauck">Christine Mauck</name>
<affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>CONRAD, Arlington, VA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>CONRAD, Arlington, VA</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cranston, Ross D" sort="Cranston, Ross D" uniqKey="Cranston R" first="Ross D." last="Cranston">Ross D. Cranston</name>
<affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Yang, Kuo" sort="Yang, Kuo" uniqKey="Yang K" first="Kuo" last="Yang">Kuo Yang</name>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Elliott, Julie" sort="Elliott, Julie" uniqKey="Elliott J" first="Julie" last="Elliott">Julie Elliott</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tanner, Karen" sort="Tanner, Karen" uniqKey="Tanner K" first="Karen" last="Tanner">Karen Tanner</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgowan, Ian" sort="Mcgowan, Ian" uniqKey="Mcgowan I" first="Ian" last="Mcgowan">Ian Mcgowan</name>
<affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kashuba, Angela" sort="Kashuba, Angela" uniqKey="Kashuba A" first="Angela" last="Kashuba">Angela Kashuba</name>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Anton, Peter A" sort="Anton, Peter A" uniqKey="Anton P" first="Peter A." last="Anton">Peter A. Anton</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Objectives</title>
<p>This study was designed to assess the dose-response relationship between tissue, blood, vaginal and rectal compartment concentrations of tenofovir (TFV) and tenofovir diphosphate (TFVdp) and <italic>ex vivo</italic>
rectal HIV suppression following oral tenofovir disoproxil fumarate (TDF) and rectal administration of TFV 1% vaginally-formulated gel.</p>
</sec>
<sec><title>Design</title>
<p>Phase 1, randomized, two-site (US), double-blind, placebo-controlled study of sexually-abstinent males and females.</p>
</sec>
<sec><title>Methods</title>
<p>Eighteen participants received a single 300 mg exposure of oral TDF and were then randomized 2∶1 to receive a single then seven-daily rectal exposures of TFV 1% gel (40 mg TFV per 4 ml gel application) or hydroxyethyl-cellulose (HEC) placebo gel. Blood and rectal biopsies were collected for pharmacokinetic TDF and TFVdp analyses and <italic>ex vivo</italic>
HIV-1 challenge.</p>
</sec>
<sec><title>Results</title>
<p>There was a significant fit for the TFVdp dose-response model for rectal tissue (<italic>p</italic>
= 0.0004), CD4<sup>+</sup>
<sub>MMC</sub>
(<italic>p</italic>
<0.0001), CD4<sup>−</sup>
<sub>MMC</sub>
(<italic>p</italic>
<0.0001), and Total<sub>MMC</sub>
(<italic>p</italic>
<0.0001) compartments with <italic>r<sup>2</sup>
</italic>
ranging 0.36–0.64. Higher concentrations of TFVdp corresponded with lower p24, consistent with drug-mediated virus suppression. The single oral treatment failed to provide adequate compartment drug exposure to reach the EC<sub>50</sub>
of rectal tissue TFVdp predicted to be necessary to suppress HIV in rectal tissue. The EC<sub>50</sub>
for CD4<sup>+</sup>
<sub>MMC</sub>
was within the single topical treatment range, providing evidence that a 1% topical, vaginally-formulated TFV gel provided <italic>in-vivo</italic>
doses predicted to provide for 50% efficacy in the <italic>ex vivo</italic>
assay. The 7-daily topical TFV gel treatment provided TFVdp concentrations that reached EC<sub>90</sub>
biopsy efficacy for CD4<sup>−</sup>
<sub>MMC</sub>
, CD4<sup>+</sup>
<sub>MMC</sub>
and Total<sub>MMC</sub>
compartments.</p>
</sec>
<sec><title>Conclusion</title>
<p>The TFVdp MMC compartment (CD4+, CD4− and Total) provided the best surrogate for biopsy infectibility and the 7-daily topical TFV gel treatment provided the strongest PK profile for HIV suppression.</p>
</sec>
<sec><title></title>
<p>ClinicalTrials.gov <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov/ct2/show/NCT00984971">NCT00984971.</ext-link>
</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abner, Sr" uniqKey="Abner S">SR Abner</name>
</author>
<author><name sortKey="Guenthner, Pc" uniqKey="Guenthner P">PC Guenthner</name>
</author>
<author><name sortKey="Guarner, J" uniqKey="Guarner J">J Guarner</name>
</author>
<author><name sortKey="Hancock, Ka" uniqKey="Hancock K">KA Hancock</name>
</author>
<author><name sortKey="Cummins, Je" uniqKey="Cummins J">JE Cummins</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Batman, Pa" uniqKey="Batman P">PA Batman</name>
</author>
<author><name sortKey="Fleming, Sc" uniqKey="Fleming S">SC Fleming</name>
</author>
<author><name sortKey="Sedgwick, Pm" uniqKey="Sedgwick P">PM Sedgwick</name>
</author>
<author><name sortKey="Macdonald, Tt" uniqKey="Macdonald T">TT MacDonald</name>
</author>
<author><name sortKey="Griffin, Ge" uniqKey="Griffin G">GE Griffin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fischetti, L" uniqKey="Fischetti L">L Fischetti</name>
</author>
<author><name sortKey="Barry, Sm" uniqKey="Barry S">SM Barry</name>
</author>
<author><name sortKey="Hope, Tj" uniqKey="Hope T">TJ Hope</name>
</author>
<author><name sortKey="Shattock, Rj" uniqKey="Shattock R">RJ Shattock</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Greenhead, P" uniqKey="Greenhead P">P Greenhead</name>
</author>
<author><name sortKey="Hayes, P" uniqKey="Hayes P">P Hayes</name>
</author>
<author><name sortKey="Watts, Ps" uniqKey="Watts P">PS Watts</name>
</author>
<author><name sortKey="Laing, Kg" uniqKey="Laing K">KG Laing</name>
</author>
<author><name sortKey="Griffin, Ge" uniqKey="Griffin G">GE Griffin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hladik, F" uniqKey="Hladik F">F Hladik</name>
</author>
<author><name sortKey="Doncel, Gf" uniqKey="Doncel G">GF Doncel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anton, Pa" uniqKey="Anton P">PA Anton</name>
</author>
<author><name sortKey="Cranston, Rd" uniqKey="Cranston R">RD Cranston</name>
</author>
<author><name sortKey="Kashuba, A" uniqKey="Kashuba A">A Kashuba</name>
</author>
<author><name sortKey="Hendrix, Cw" uniqKey="Hendrix C">CW Hendrix</name>
</author>
<author><name sortKey="Bumpus, Nn" uniqKey="Bumpus N">NN Bumpus</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anton, Pa" uniqKey="Anton P">PA Anton</name>
</author>
<author><name sortKey="Saunders, T" uniqKey="Saunders T">T Saunders</name>
</author>
<author><name sortKey="Elliott, J" uniqKey="Elliott J">J Elliott</name>
</author>
<author><name sortKey="Khanukhova, E" uniqKey="Khanukhova E">E Khanukhova</name>
</author>
<author><name sortKey="Dennis, R" uniqKey="Dennis R">R Dennis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Richardson Harman, N" uniqKey="Richardson Harman N">N Richardson-Harman</name>
</author>
<author><name sortKey="Mauck, C" uniqKey="Mauck C">C Mauck</name>
</author>
<author><name sortKey="Mcgowan, I" uniqKey="Mcgowan I">I McGowan</name>
</author>
<author><name sortKey="Anton, P" uniqKey="Anton P">P Anton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tien, D" uniqKey="Tien D">D Tien</name>
</author>
<author><name sortKey="Schnaare, Rl" uniqKey="Schnaare R">RL Schnaare</name>
</author>
<author><name sortKey="Kang, F" uniqKey="Kang F">F Kang</name>
</author>
<author><name sortKey="Cohl, G" uniqKey="Cohl G">G Cohl</name>
</author>
<author><name sortKey="Mccormick, Tj" uniqKey="Mccormick T">TJ McCormick</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hendrix, Cw" uniqKey="Hendrix C">CW Hendrix</name>
</author>
<author><name sortKey="Chen, Ba" uniqKey="Chen B">BA Chen</name>
</author>
<author><name sortKey="Guddera, V" uniqKey="Guddera V">V Guddera</name>
</author>
<author><name sortKey="Hoesley, C" uniqKey="Hoesley C">C Hoesley</name>
</author>
<author><name sortKey="Justman, J" uniqKey="Justman J">J Justman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anton, Pa" uniqKey="Anton P">PA Anton</name>
</author>
<author><name sortKey="Elliott, J" uniqKey="Elliott J">J Elliott</name>
</author>
<author><name sortKey="Poles, Ma" uniqKey="Poles M">MA Poles</name>
</author>
<author><name sortKey="Mcgowan, Im" uniqKey="Mcgowan I">IM McGowan</name>
</author>
<author><name sortKey="Matud, J" uniqKey="Matud J">J Matud</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fletcher, Ps" uniqKey="Fletcher P">PS Fletcher</name>
</author>
<author><name sortKey="Elliott, J" uniqKey="Elliott J">J Elliott</name>
</author>
<author><name sortKey="Grivel, Jc" uniqKey="Grivel J">JC Grivel</name>
</author>
<author><name sortKey="Margolis, L" uniqKey="Margolis L">L Margolis</name>
</author>
<author><name sortKey="Anton, P" uniqKey="Anton P">P Anton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Richardson Harman, N" uniqKey="Richardson Harman N">N Richardson-Harman</name>
</author>
<author><name sortKey="Lackman Smith, C" uniqKey="Lackman Smith C">C Lackman-Smith</name>
</author>
<author><name sortKey="Fletcher, Ps" uniqKey="Fletcher P">PS Fletcher</name>
</author>
<author><name sortKey="Anton, Pa" uniqKey="Anton P">PA Anton</name>
</author>
<author><name sortKey="Bremer, Jw" uniqKey="Bremer J">JW Bremer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Glatting, G" uniqKey="Glatting G">G Glatting</name>
</author>
<author><name sortKey="Kletting, P" uniqKey="Kletting P">P Kletting</name>
</author>
<author><name sortKey="Reske, Sn" uniqKey="Reske S">SN Reske</name>
</author>
<author><name sortKey="Hohl, K" uniqKey="Hohl K">K Hohl</name>
</author>
<author><name sortKey="Ring, C" uniqKey="Ring C">C Ring</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yang, K H" uniqKey="Yang K">K-H Yang</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Tebit, Dm" uniqKey="Tebit D">DM Tebit</name>
</author>
<author><name sortKey="Ndembi, N" uniqKey="Ndembi N">N Ndembi</name>
</author>
<author><name sortKey="Weinberg, A" uniqKey="Weinberg A">A Weinberg</name>
</author>
<author><name sortKey="Quinones Mateu, Me" uniqKey="Quinones Mateu M">ME Quinones-Mateu</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
</pmc>
<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Correlation between compartmental tenofovir concentrations and an ex vivo rectal biopsy model of tissue infectibility in the RMP-02/MTN-006 phase 1 study.</title>
<author><name sortKey="Richardson Harman, Nicola" sort="Richardson Harman, Nicola" uniqKey="Richardson Harman N" first="Nicola" last="Richardson-Harman">Nicola Richardson-Harman</name>
<affiliation wicri:level="2"><nlm:affiliation>Alpha StatConsult, LLC, Damascus, MD, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Alpha StatConsult, LLC, Damascus, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hendrix, Craig W" sort="Hendrix, Craig W" uniqKey="Hendrix C" first="Craig W" last="Hendrix">Craig W. Hendrix</name>
<affiliation wicri:level="2"><nlm:affiliation>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bumpus, Namandje N" sort="Bumpus, Namandje N" uniqKey="Bumpus N" first="Namandjé N" last="Bumpus">Namandjé N. Bumpus</name>
<affiliation wicri:level="2"><nlm:affiliation>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mauck, Christine" sort="Mauck, Christine" uniqKey="Mauck C" first="Christine" last="Mauck">Christine Mauck</name>
<affiliation wicri:level="2"><nlm:affiliation>CONRAD, Arlington, VA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>CONRAD, Arlington, VA</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cranston, Ross D" sort="Cranston, Ross D" uniqKey="Cranston R" first="Ross D" last="Cranston">Ross D. Cranston</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Yang, Kuo" sort="Yang, Kuo" uniqKey="Yang K" first="Kuo" last="Yang">Kuo Yang</name>
<affiliation wicri:level="4"><nlm:affiliation>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Elliott, Julie" sort="Elliott, Julie" uniqKey="Elliott J" first="Julie" last="Elliott">Julie Elliott</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tanner, Karen" sort="Tanner, Karen" uniqKey="Tanner K" first="Karen" last="Tanner">Karen Tanner</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgowan, Ian" sort="Mcgowan, Ian" uniqKey="Mcgowan I" first="Ian" last="Mcgowan">Ian Mcgowan</name>
<affiliation wicri:level="2"><nlm:affiliation>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kashuba, Angela" sort="Kashuba, Angela" uniqKey="Kashuba A" first="Angela" last="Kashuba">Angela Kashuba</name>
<affiliation wicri:level="4"><nlm:affiliation>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Anton, Peter A" sort="Anton, Peter A" uniqKey="Anton P" first="Peter A" last="Anton">Peter A. Anton</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2014">2014</date>
<idno type="RBID">pubmed:25350130</idno>
<idno type="pmid">25350130</idno>
<idno type="doi">10.1371/journal.pone.0111507</idno>
<idno type="wicri:Area/PubMed/Corpus">001807</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001807</idno>
<idno type="wicri:Area/PubMed/Curation">001800</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001800</idno>
<idno type="wicri:Area/PubMed/Checkpoint">001800</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001800</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Correlation between compartmental tenofovir concentrations and an ex vivo rectal biopsy model of tissue infectibility in the RMP-02/MTN-006 phase 1 study.</title>
<author><name sortKey="Richardson Harman, Nicola" sort="Richardson Harman, Nicola" uniqKey="Richardson Harman N" first="Nicola" last="Richardson-Harman">Nicola Richardson-Harman</name>
<affiliation wicri:level="2"><nlm:affiliation>Alpha StatConsult, LLC, Damascus, MD, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Alpha StatConsult, LLC, Damascus, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hendrix, Craig W" sort="Hendrix, Craig W" uniqKey="Hendrix C" first="Craig W" last="Hendrix">Craig W. Hendrix</name>
<affiliation wicri:level="2"><nlm:affiliation>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bumpus, Namandje N" sort="Bumpus, Namandje N" uniqKey="Bumpus N" first="Namandjé N" last="Bumpus">Namandjé N. Bumpus</name>
<affiliation wicri:level="2"><nlm:affiliation>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Medicine and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mauck, Christine" sort="Mauck, Christine" uniqKey="Mauck C" first="Christine" last="Mauck">Christine Mauck</name>
<affiliation wicri:level="2"><nlm:affiliation>CONRAD, Arlington, VA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>CONRAD, Arlington, VA</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cranston, Ross D" sort="Cranston, Ross D" uniqKey="Cranston R" first="Ross D" last="Cranston">Ross D. Cranston</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Yang, Kuo" sort="Yang, Kuo" uniqKey="Yang K" first="Kuo" last="Yang">Kuo Yang</name>
<affiliation wicri:level="4"><nlm:affiliation>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Elliott, Julie" sort="Elliott, Julie" uniqKey="Elliott J" first="Julie" last="Elliott">Julie Elliott</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tanner, Karen" sort="Tanner, Karen" uniqKey="Tanner K" first="Karen" last="Tanner">Karen Tanner</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgowan, Ian" sort="Mcgowan, Ian" uniqKey="Mcgowan I" first="Ian" last="Mcgowan">Ian Mcgowan</name>
<affiliation wicri:level="2"><nlm:affiliation>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Magee-Womens Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kashuba, Angela" sort="Kashuba, Angela" uniqKey="Kashuba A" first="Angela" last="Kashuba">Angela Kashuba</name>
<affiliation wicri:level="4"><nlm:affiliation>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Anton, Peter A" sort="Anton, Peter A" uniqKey="Anton P" first="Peter A" last="Anton">Peter A. Anton</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for HIV Prevention Research, UCLA AIDS Institute, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PloS one</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Oral</term>
<term>Administration, Rectal</term>
<term>Adult</term>
<term>Biopsy</term>
<term>Cellulose (analogs & derivatives)</term>
<term>Cellulose (chemistry)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Gels</term>
<term>HIV Infections (prevention & control)</term>
<term>Humans</term>
<term>Male</term>
<term>Rectum (drug effects)</term>
<term>Tenofovir (administration & dosage)</term>
<term>Tenofovir (pharmacokinetics)</term>
<term>Vaginal Creams, Foams, and Jellies (chemistry)</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Administration par voie orale</term>
<term>Administration par voie rectale</term>
<term>Adulte</term>
<term>Biopsie</term>
<term>Cellulose ()</term>
<term>Cellulose (analogues et dérivés)</term>
<term>Crèmes, mousses et gels vaginaux ()</term>
<term>Femelle</term>
<term>Gels</term>
<term>Humains</term>
<term>Infections à VIH ()</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Méthode en double aveugle</term>
<term>Rectum ()</term>
<term>Relation dose-effet des médicaments</term>
<term>Ténofovir (administration et posologie)</term>
<term>Ténofovir (pharmacocinétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Tenofovir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Cellulose</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cellulose</term>
<term>Vaginal Creams, Foams, and Jellies</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Ténofovir</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Cellulose</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Rectum</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Ténofovir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Tenofovir</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>HIV Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Administration, Oral</term>
<term>Administration, Rectal</term>
<term>Adult</term>
<term>Biopsy</term>
<term>Dose-Response Relationship, Drug</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Gels</term>
<term>Humans</term>
<term>Male</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Administration par voie orale</term>
<term>Administration par voie rectale</term>
<term>Adulte</term>
<term>Biopsie</term>
<term>Cellulose</term>
<term>Crèmes, mousses et gels vaginaux</term>
<term>Femelle</term>
<term>Gels</term>
<term>Humains</term>
<term>Infections à VIH</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Méthode en double aveugle</term>
<term>Rectum</term>
<term>Relation dose-effet des médicaments</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">This study was designed to assess the dose-response relationship between tissue, blood, vaginal and rectal compartment concentrations of tenofovir (TFV) and tenofovir diphosphate (TFVdp) and ex vivo rectal HIV suppression following oral tenofovir disoproxil fumarate (TDF) and rectal administration of TFV 1% vaginally-formulated gel.</div>
</front>
</TEI>
</pubmed>
</double>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Amérique/explor/PittsburghV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003C10 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 003C10 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Amérique |area= PittsburghV1 |flux= Ncbi |étape= Merge |type= RBID |clé= PMC:4211741 |texte= Correlation between Compartmental Tenofovir Concentrations and an Ex Vivo Rectal Biopsy Model of Tissue Infectibility in the RMP-02/MTN-006 Phase 1 Study }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:25350130" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \ | NlmPubMed2Wicri -a PittsburghV1
This area was generated with Dilib version V0.6.38. |