Fundamental aspects of long-acting tenofovir alafenamide delivery from subdermal implants for HIV prophylaxis

Global efforts aimed at preventing human immunodeficiency virus type one (HIV-1) infection in vulnerable populations appear to be stalling, limiting our ability to control the epidemic. Long-acting, controlled drug administration from subdermal implants holds significant potential by reducing the co...

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Veröffentlicht in:Scientific reports Jg. 12; H. 1; S. 8224 - 25
Hauptverfasser: Gunawardana, Manjula, Remedios-Chan, Mariana, Sanchez, Debbie, Webster, Simon, Castonguay, Amalia E., Webster, Paul, Buser, Christopher, Moss, John A., Trinh, MyMy, Beliveau, Martin, Hendrix, Craig W., Marzinke, Mark A., Tuck, Michael, Caprioli, Richard M., Reyzer, Michelle L., Kuo, Joseph, Gallay, Philippe A., Baum, Marc M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 17.05.2022
Nature Publishing Group
Nature Portfolio
Schlagworte:
631/154/152
692/308/153
Adenine
Alanine - therapeutic use
Animal models
Animals
Anti-HIV Agents
Antiretroviral drugs
At risk populations
Dosage
Drug dosages
Female
HIV
HIV Infections - drug therapy
HIV Infections - prevention & control
Human immunodeficiency virus
Humanities and Social Sciences
Mass spectrometry
Mass spectroscopy
Metabolites
Mice
multidisciplinary
Pharmacokinetics
Pharmacology
Prophylaxis
Science
Science (multidisciplinary)
Spatial distribution
Tenofovir
Tenofovir - analogs & derivatives
Tenofovir - therapeutic use
Transplants & implants
ISSN:2045-2322, 2045-2322
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Abstract Global efforts aimed at preventing human immunodeficiency virus type one (HIV-1) infection in vulnerable populations appear to be stalling, limiting our ability to control the epidemic. Long-acting, controlled drug administration from subdermal implants holds significant potential by reducing the compliance burden associated with frequent dosing. We, and others, are exploring the development of complementary subdermal implant technologies delivering the potent prodrug, tenofovir alafenamide (TAF). The current report addresses knowledge gaps in the preclinical pharmacology of long-acting, subdermal TAF delivery using several mouse models. Systemic drug disposition during TAF implant dosing was explained by a multi-compartment pharmacokinetic (PK) model. Imaging mass spectrometry was employed to characterize the spatial distribution of TAF and its principal five metabolites in local tissues surrounding the implant. Humanized mouse studies determined the effective TAF dose for preventing vaginal and rectal HIV-1 acquisition. Our results represent an important step in the development of a safe and effective TAF implant for HIV-1 prevention.
AbstractList Global efforts aimed at preventing human immunodeficiency virus type one (HIV-1) infection in vulnerable populations appear to be stalling, limiting our ability to control the epidemic. Long-acting, controlled drug administration from subdermal implants holds significant potential by reducing the compliance burden associated with frequent dosing. We, and others, are exploring the development of complementary subdermal implant technologies delivering the potent prodrug, tenofovir alafenamide (TAF). The current report addresses knowledge gaps in the preclinical pharmacology of long-acting, subdermal TAF delivery using several mouse models. Systemic drug disposition during TAF implant dosing was explained by a multi-compartment pharmacokinetic (PK) model. Imaging mass spectrometry was employed to characterize the spatial distribution of TAF and its principal five metabolites in local tissues surrounding the implant. Humanized mouse studies determined the effective TAF dose for preventing vaginal and rectal HIV-1 acquisition. Our results represent an important step in the development of a safe and effective TAF implant for HIV-1 prevention.
Global efforts aimed at preventing human immunodeficiency virus type one (HIV-1) infection in vulnerable populations appear to be stalling, limiting our ability to control the epidemic. Long-acting, controlled drug administration from subdermal implants holds significant potential by reducing the compliance burden associated with frequent dosing. We, and others, are exploring the development of complementary subdermal implant technologies delivering the potent prodrug, tenofovir alafenamide (TAF). The current report addresses knowledge gaps in the preclinical pharmacology of long-acting, subdermal TAF delivery using several mouse models. Systemic drug disposition during TAF implant dosing was explained by a multi-compartment pharmacokinetic (PK) model. Imaging mass spectrometry was employed to characterize the spatial distribution of TAF and its principal five metabolites in local tissues surrounding the implant. Humanized mouse studies determined the effective TAF dose for preventing vaginal and rectal HIV-1 acquisition. Our results represent an important step in the development of a safe and effective TAF implant for HIV-1 prevention.Global efforts aimed at preventing human immunodeficiency virus type one (HIV-1) infection in vulnerable populations appear to be stalling, limiting our ability to control the epidemic. Long-acting, controlled drug administration from subdermal implants holds significant potential by reducing the compliance burden associated with frequent dosing. We, and others, are exploring the development of complementary subdermal implant technologies delivering the potent prodrug, tenofovir alafenamide (TAF). The current report addresses knowledge gaps in the preclinical pharmacology of long-acting, subdermal TAF delivery using several mouse models. Systemic drug disposition during TAF implant dosing was explained by a multi-compartment pharmacokinetic (PK) model. Imaging mass spectrometry was employed to characterize the spatial distribution of TAF and its principal five metabolites in local tissues surrounding the implant. Humanized mouse studies determined the effective TAF dose for preventing vaginal and rectal HIV-1 acquisition. Our results represent an important step in the development of a safe and effective TAF implant for HIV-1 prevention.
Abstract Global efforts aimed at preventing human immunodeficiency virus type one (HIV-1) infection in vulnerable populations appear to be stalling, limiting our ability to control the epidemic. Long-acting, controlled drug administration from subdermal implants holds significant potential by reducing the compliance burden associated with frequent dosing. We, and others, are exploring the development of complementary subdermal implant technologies delivering the potent prodrug, tenofovir alafenamide (TAF). The current report addresses knowledge gaps in the preclinical pharmacology of long-acting, subdermal TAF delivery using several mouse models. Systemic drug disposition during TAF implant dosing was explained by a multi-compartment pharmacokinetic (PK) model. Imaging mass spectrometry was employed to characterize the spatial distribution of TAF and its principal five metabolites in local tissues surrounding the implant. Humanized mouse studies determined the effective TAF dose for preventing vaginal and rectal HIV-1 acquisition. Our results represent an important step in the development of a safe and effective TAF implant for HIV-1 prevention.
ArticleNumber 8224
Author Gallay, Philippe A.
Tuck, Michael
Sanchez, Debbie
Gunawardana, Manjula
Trinh, MyMy
Webster, Simon
Castonguay, Amalia E.
Beliveau, Martin
Hendrix, Craig W.
Caprioli, Richard M.
Reyzer, Michelle L.
Baum, Marc M.
Kuo, Joseph
Moss, John A.
Webster, Paul
Remedios-Chan, Mariana
Marzinke, Mark A.
Buser, Christopher
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  surname: Gunawardana
  fullname: Gunawardana, Manjula
  organization: Department of Chemistry, Oak Crest Institute of Science
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  givenname: Mariana
  surname: Remedios-Chan
  fullname: Remedios-Chan, Mariana
  organization: Department of Chemistry, Oak Crest Institute of Science
– sequence: 3
  givenname: Debbie
  surname: Sanchez
  fullname: Sanchez, Debbie
  organization: Department of Chemistry, Oak Crest Institute of Science
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  givenname: Simon
  surname: Webster
  fullname: Webster, Simon
  organization: Department of Chemistry, Oak Crest Institute of Science
– sequence: 5
  givenname: Amalia E.
  surname: Castonguay
  fullname: Castonguay, Amalia E.
  organization: Department of Chemistry, Oak Crest Institute of Science
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  givenname: Paul
  surname: Webster
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  organization: Department of Chemistry, Oak Crest Institute of Science
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  organization: Department of Chemistry, Oak Crest Institute of Science
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  organization: Department of Chemistry, Oak Crest Institute of Science
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  givenname: MyMy
  surname: Trinh
  fullname: Trinh, MyMy
  organization: Certara Integrated Drug Development
– sequence: 10
  givenname: Martin
  surname: Beliveau
  fullname: Beliveau, Martin
  organization: Certara Integrated Drug Development
– sequence: 11
  givenname: Craig W.
  surname: Hendrix
  fullname: Hendrix, Craig W.
  organization: Department of Medicine, Johns Hopkins University
– sequence: 12
  givenname: Mark A.
  surname: Marzinke
  fullname: Marzinke, Mark A.
  organization: Department of Medicine, Johns Hopkins University, Department of Pathology, Johns Hopkins University
– sequence: 13
  givenname: Michael
  surname: Tuck
  fullname: Tuck, Michael
  organization: Department of Biochemistry, Vanderbilt University
– sequence: 14
  givenname: Richard M.
  surname: Caprioli
  fullname: Caprioli, Richard M.
  organization: Department of Biochemistry, Vanderbilt University
– sequence: 15
  givenname: Michelle L.
  surname: Reyzer
  fullname: Reyzer, Michelle L.
  organization: Department of Biochemistry, Vanderbilt University
– sequence: 16
  givenname: Joseph
  surname: Kuo
  fullname: Kuo, Joseph
  organization: Department of Immunology & Microbiology, The Scripps Research Institute
– sequence: 17
  givenname: Philippe A.
  surname: Gallay
  fullname: Gallay, Philippe A.
  organization: Department of Immunology & Microbiology, The Scripps Research Institute
– sequence: 18
  givenname: Marc M.
  surname: Baum
  fullname: Baum, Marc M.
  email: m.baum@oak-crest.org
  organization: Department of Chemistry, Oak Crest Institute of Science
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35581262$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_3390_pathogens14070645
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Cites_doi 10.3390/pharmaceutics11070315
10.1128/aac.00968-06
10.1056/NEJMoa1011205
10.1016/j.jconrel.2018.08.010
10.1007/s11095-020-2777-2
10.1016/j.jprot.2014.03.021
10.1016/0065-2571(84)90007-4
10.3390/pharmaceutics12111057
10.1128/aac.00930-20
10.1097/qad.0000000000000979
10.1080/0049825042000205540
10.1080/0049825042000205540a
10.1097/coh.0000000000000002
10.1128/AAC.04954-14
10.1056/NEJMoa1108524
10.1097/QAI.0b013e31826f9962
10.1002/cpt.1227
10.2174/1874357901812010001
10.3851/imp2770
10.1021/acs.analchem.5b03794
10.1016/S0140-6736(13)61127-7
10.1128/aac.04952-14
10.1016/s0140-6736(15)00056-2
10.1124/jpet.118.250357
10.1021/bi301519p
10.1128/AAC.00597-11
10.1128/AAC.00656-15
10.1124/mol.108.045526
10.1128/aac.01834-15
10.1097/OLQ.0b013e3181cbf77d
10.1002/jps.24154
10.1056/NEJMoa1506273
10.3390/pharmaceutics12100981
10.1021/acsptsci.0c00015
10.1016/j.jpba.2018.02.011
10.1016/j.antiviral.2015.11.009
10.1056/NEJMoa2101016
10.1371/journal.pone.0055013
10.1371/journal.pone.0008829
10.1021/acs.analchem.5b04409
10.1038/nbt.3462
10.1089/aid.2021.0028
10.1007/s11095-017-2255-7
10.1093/infdis/jiab152
10.1126/scitranslmed.aap8758
10.1021/cr3004295
10.1016/j.tim.2012.03.007
10.1021/mp3002045
10.1126/scitranslmed.3004006
10.1126/science.1193748
10.1177/1060028021995586
10.1007/s10461-015-0997-y
10.3389/fphar.2020.569373
10.1007/s11095-016-1904-6
10.1007/s11096-013-9861-1
10.1371/journal.pone.0184303
10.1136/jcp.34.10.1083
10.1097/QAI.0000000000000314
10.1038/nm0414-323
10.1007/s10461-013-0429-9
10.1097/QAI.0000000000001129
10.1371/journal.pone.0040382
10.1128/AAC.01893-19
10.1136/bmjopen-2021-052880
10.1592/phco.23.6.695.32189
10.1089/aid.2013.0044
10.1056/NEJMoa1110711
10.1038/s41598-020-69937-5
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References BirkusGCathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131Antimicrob. Agents Chemother.2007515435501:CAS:528:DC%2BD2sXhsVOqu70%3D10.1128/aac.00968-0617145787
RobbinsBLWilcoxCKFridlandARodmanJHMetabolism of tenofovir and didanosine in quiescent or stimulated human peripheral blood mononuclear cellsPharmacotherapy2003236957011:CAS:528:DC%2BD3sXltVyjur0%3D10.1592/phco.23.6.695.3218912820810
GunawardanaMBaumMMSmithTJMossJAAn intravaginal ring for the sustained delivery of antibodiesJ. Pharm. Sci.2014103361136201:CAS:528:DC%2BC2cXhslOkurvL10.1002/jps.24154252311934206599
RosenEPAnalysis of antiretrovirals in single hair strands for evaluation of drug adherence with infrared-matrix-assisted laser desorption electrospray ionization mass spectrometry imagingAnal. Chem.201688133613441:CAS:528:DC%2BC2MXitVGrsrfF10.1021/acs.analchem.5b0379426688545
LouissaintNASingle dose pharmacokinetics of oral tenofovir in plasma, peripheral blood mononuclear cells, colonic tissue, and vaginal tissueAIDS Res. Hum. Retroviruses201329144314501:CAS:528:DC%2BC3sXhs1ylsbbK10.1089/aid.2013.0044236003653809387
GesselMMNorrisJLCaprioliRMMALDI imaging mass spectrometry: Spatial molecular analysis to enable a new age of discoveryJ. Proteomics201410771821:CAS:528:DC%2BC2cXmtVWrtLc%3D10.1016/j.jprot.2014.03.02124686089
ChouTCTalalayPQuantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitorsAdv. Enzyme Regul.19842227551:CAS:528:DyaL2cXktlaksLk%3D10.1016/0065-2571(84)90007-46382953
McCormackSPre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): Effectiveness results from the pilot phase of a pragmatic open-label randomised trialLancet2016387536010.1016/s0140-6736(15)00056-2263642634700047
Abdool KarimQEffectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in womenScience2010329116811742010Sci...329.1168A1:CAS:528:DC%2BC3cXhtV2hsr%2FI10.1126/science.1193748206439153001187
Hare, C. B. et al. in 2019 Conference on Retroviruses and Opportunistic Infections (CROI). Abstract Number 104 (CROI, Alexandria, VA).
SpreenWRMargolisDAPottageJCLong-acting Injectable antiretrovirals for HIV treatment and preventionCurr. Opin. HIV AIDS201385655711:CAS:528:DC%2BC3sXhs1WltrfF10.1097/coh.0000000000000002241008773815009
JavanbakhtMPrevalence and correlates of heterosexual anal intercourse among clients attending public sexually transmitted disease clinics in Los Angeles CountySex. Transm. Dis.20103736937610.1097/OLQ.0b013e3181cbf77d20514690
HendrixCWMTN-001: Randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartmentsPLoS ONE20138e550132013PLoSO...855013H1:CAS:528:DC%2BC3sXis1art70%3D10.1371/journal.pone.0055013233830373559346
SeneviratneHKHamlinANHeckCJSBumpusNNSpatial distribution profiles of emtricitabine, tenofovir, efavirenz, and rilpivirine in murine tissues following in vivo dosing correlate with their safety profiles in humansACS Pharmacol. Transl. Sci.202036556651:CAS:528:DC%2BB3cXnslehsLc%3D10.1021/acsptsci.0c0001532832868
GorbachPMOrder of orifices: Sequence of condom use and ejaculation by orifice during anal intercourse among women: implications for HIV transmissionJ. Acquir. Immune Defic. Syndr.20146742442910.1097/QAI.0000000000000314253567784217134
BirkusGIntracellular activation of tenofovir alafenamide and the effect of viral and host protease inhibitorsAntimicrob. Agents Chemother.2016603163221:CAS:528:DC%2BC28XhtVCrs7nP10.1128/aac.01834-1526503655
HummertPParsonsTLEnsignLMHoangTMarzinkeMAValidation and implementation of liquid chromatographic-mass spectrometric (LC-MS) methods for the quantification of tenofovir prodrugsJ. Pharm. Biomed. Anal.20181522482561:CAS:528:DC%2BC1cXis1aqt7w%3D10.1016/j.jpba.2018.02.011294330975835418
HendrixCWHIV antiretroviral pre-exposure prophylaxis: Development challenges and pipeline promiseClin. Pharmacol. Ther.20181041082109710.1002/cpt.122730199098
WardKWPreclinical pharmacokinetics and interspecies scaling of a novel vitronectin receptor antagonistDrug. Metab. Dispos.199927123212411:CAS:528:DyaK1MXntFShtro%3D10534306
AngelPMCaprioliRMMatrix-assisted laser desorption ionization imaging mass spectrometry: In Situ molecular mappingBiochemistry201352381838281:CAS:528:DC%2BC38XhvVygu7zK10.1021/bi301519p23259809
UNAIDS. Global Factsheet 2017, <AIDSinfo.unaids.org> (2018).
DentonPWSystemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT micePLoS ONE20105e88292010PLoSO...5.8829D1:CAS:528:DC%2BC3cXht1emtrk%3D10.1371/journal.pone.0008829200986232809117
AndersonPLEmtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with menSci. Transl. Med.201241511:CAS:528:DC%2BC38XhsFOkurvI10.1126/scitranslmed.3004006
Pons-FaudoaFPViral load reduction in SHIV-positive nonhuman primates via long-acting subcutaneous tenofovir alafenamide fumarate release from a nanofluidic implantPharmaceutics202010.3390/pharmaceutics12100981330807767590004
WardKWHardyLBKehlerJRAzzaranoLMSmithBRApparent absolute oral bioavailability in excess of 100% for a vitronectin receptor antagonist (SB-265123) in Rat. II. Studies implicating transporter-mediated intestinal secretionXenobiotica2004343673771:CAS:528:DC%2BD2cXjsF2jurY%3D10.1080/0049825042000205540a15268981
Hendrix, C. W. in 2014 Conference on Retroviruses and Opportunistic Infections (CROI). Oral Abstract 61 (CROI, Alexandria, VA).
DurhamSHChahineEBCabotegravir-rilpivirine: The first complete long-acting injectable regimen for the treatment of HIV-1 infectionAnn. Pharmacother.202110.1177/106002802199558633593093
SeneviratneHKHendrixCWFuchsEJBumpusNNMALDI mass spectrometry imaging reveals heterogeneous distribution of tenofovir and tenofovir diphosphate in colorectal tissue of subjects receiving a tenofovir-containing enemaJ. Pharmacol. Exp. Ther.201836740481:CAS:528:DC%2BC1cXitVegsLzF10.1124/jpet.118.250357300378136123665
UNAIDS. 90-90-0: An Ambitious Treatment Target to Help End the AIDS Epidemic. Report No. UNAIDS/JC2684, 40 (UNAIDS, Geneva, CH, 2014).
BaumMMHighly synergistic drug combination prevents vaginal HIV infection in humanized miceSci. Rep.202010129952020NatSR..1012995B1:CAS:528:DC%2BB3cXhsFers7vP10.1038/s41598-020-69937-5327476827400648
GallayPAProtection efficacy of C5A against vaginal and rectal HIV challenges in humanized miceOpen Virol. J.2018121131:CAS:528:DC%2BC1MXktlyqsrc%3D10.2174/1874357901812010001295412735842390
BamRAYantSRCihlarTTenofovir alafenamide is not a substrate for renal organic anion transporters (OATs) and does not exhibit OAT-dependent cytotoxicityAntivir. Ther.2014196876921:CAS:528:DC%2BC2MXisVOguro%3D10.3851/imp277024699134
RomanoJWTenofovir alafenamide for HIV prevention: Review of the proceedings from the gates foundation long-acting TAF product development meetingAIDS Res. Hum. Retroviruses2021374094201:CAS:528:DC%2BB3MXht1WrsLbL10.1089/aid.2021.0028339137608213003
PrathipatiPKMandalSPonGVivekanandanRDestacheCJPharmacokinetic and tissue distribution profile of long acting tenofovir alafenamide and elvitegravir loaded nanoparticles in humanized mice modelPharm. Res.201734274927551:CAS:528:DC%2BC2sXhsVyqsrjE10.1007/s11095-017-2255-7289051735738272
MolinaJMOn-demand preexposure prophylaxis in men at high risk for HIV-1 infectionN. Engl. J. Med.2015373223722461:CAS:528:DC%2BC28XntFSnsLc%3D10.1056/NEJMoa150627326624850
ChuaCYXTranscutaneously refillable nanofluidic implant achieves sustained level of tenofovir diphosphate for HIV pre-exposure prophylaxisJ. Control. Release20182863153251:CAS:528:DC%2BC1cXhsVKqsrvN10.1016/j.jconrel.2018.08.010300922546345255
MuchombaFMGearingRESimoniJMEl-BasselNState of the science of adherence in pre-exposure prophylaxis and microbicide trialsJAIDS2012614904981:CAS:528:DC%2BC38Xhs1entb3K10.1097/QAI.0b013e31826f996222932322
KellerMJA phase 1 randomized placebo-controlled safety and pharmacokinetic trial of a tenofovir disoproxil fumarate vaginal ringAIDS2016307437511:CAS:528:DC%2BC28XjsFGmurc%3D10.1097/qad.000000000000097926605514
NorrisJLCaprioliRMAnalysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical researchChem. Rev.2013113230923421:CAS:528:DC%2BC3sXit1Ght7w%3D10.1021/cr3004295233941643624074
SuJTA Subcutaneous implant of tenofovir alafenamide fumarate causes local inflammation and tissue necrosis in rabbits and macaquesAntimicrob. Agents Chemother.201910.1128/AAC.01893-19315270246879226
ChumbleyCWAbsolute quantitative MALDI imaging mass spectrometry: A case of rifampicin in liver tissuesAnal. Chem.201688239223981:CAS:528:DC%2BC28Xhtlymsr0%3D10.1021/acs.analchem.5b04409268146655080977
MossJIn vitro-in vivo and in vivo-in vivo correlations of TAF release from a novel subdermal implantAIDS Res. Hum. Retrovir.201834359359
DuwalSSchütteCvon KleistMPharmacokinetics and pharmacodynamics of the reverse transcriptase inhibitor tenofovir and prophylactic efficacy against HIV-1 infectionPLoS ONE20127e403822012PLoSO...740382D1:CAS:528:DC%2BC38XhtVKrsrzJ10.1371/journal.pone.0040382228081483394807
SimpsonSMDesign of a drug-eluting subcutaneous implant of the antiretroviral tenofovir alafenamide fumaratePharm. Res.202037831:CAS:528:DC%2BB3cXntFOqsb8%3D10.1007/s11095-020-2777-2322969517160069
ChapmanEHKurecASDaveyFRCell volumes of normal and malignant mononuclear cellsJ. Clin. Pathol.198134108310901:STN:280:DyaL38%2Fns1Wrtw%3D%3D10.1136/jcp.34.10.10836975780494369
OwenBNPrevalence and frequency of heterosexual anal intercourse among young people: A systematic review and meta-analysisAIDS Behav.2015191338136010.1007/s10461-015-0997-y25618257
BabusisDPhanTKLeeWAWatkinsWJRayASMechanism for effective lymphoid cell and tissue loading following oral administration of nucleotide prodrug GS-7340Mol. Pharmaceut.20
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References_xml – reference: MolinaJMOn-demand preexposure prophylaxis in men at high risk for HIV-1 infectionN. Engl. J. Med.2015373223722461:CAS:528:DC%2BC28XntFSnsLc%3D10.1056/NEJMoa150627326624850
– reference: DentonPWGarciaJVMucosal HIV-1 transmission and prevention strategies in BLT humanized miceTrends Microbiol.2012202682741:CAS:528:DC%2BC38XlsFCqsb8%3D10.1016/j.tim.2012.03.007225036373680353
– reference: AngelPMCaprioliRMMatrix-assisted laser desorption ionization imaging mass spectrometry: In Situ molecular mappingBiochemistry201352381838281:CAS:528:DC%2BC38XhvVygu7zK10.1021/bi301519p23259809
– reference: OwenBNPrevalence and frequency of heterosexual anal intercourse among young people: A systematic review and meta-analysisAIDS Behav.2015191338136010.1007/s10461-015-0997-y25618257
– reference: National Research Council. Guide for the Care and Use of Laboratory Animals 8th edn, Vol. 220 (The National Academies Press, 2001).
– reference: McCormackSPre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): Effectiveness results from the pilot phase of a pragmatic open-label randomised trialLancet2016387536010.1016/s0140-6736(15)00056-2263642634700047
– reference: ParsonsTLGwendenKNMarzinkeMAInterspecies differences in tenofovir alafenamide fumarate stability in plasmaAntimicrob. Agents Chemother.202010.1128/aac.00930-20328167297577166
– reference: NuttallJThe Pharmacokinetics of tenofovir following intravaginal and intrarectal administration of tenofovir gel to rhesus macaquesAntimicrob. Agents Chemother.2012561031091:CAS:528:DC%2BC38Xjt1Glug%3D%3D10.1128/AAC.00597-11219868233256015
– reference: RobbinsBLWilcoxCKFridlandARodmanJHMetabolism of tenofovir and didanosine in quiescent or stimulated human peripheral blood mononuclear cellsPharmacotherapy2003236957011:CAS:528:DC%2BD3sXltVyjur0%3D10.1592/phco.23.6.695.3218912820810
– reference: JavanbakhtMPrevalence and correlates of heterosexual anal intercourse among clients attending public sexually transmitted disease clinics in Los Angeles CountySex. Transm. Dis.20103736937610.1097/OLQ.0b013e3181cbf77d20514690
– reference: MossJIn vitro-in vivo and in vivo-in vivo correlations of TAF release from a novel subdermal implantAIDS Res. Hum. Retrovir.201834359359
– reference: ChouTCTalalayPQuantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitorsAdv. Enzyme Regul.19842227551:CAS:528:DyaL2cXktlaksLk%3D10.1016/0065-2571(84)90007-46382953
– reference: DolginELong-acting HIV drugs advanced to overcome adherence challengeNat. Med.2014203233241:CAS:528:DC%2BC2cXls1KisLY%3D10.1038/nm0414-32324710366
– reference: HoltJDThe sheep as a model of preclinical safety and pharmacokinetic evaluations of candidate microbicidesAntimicrob. Agents Chemother.201559376137701:CAS:528:DC%2BC2MXhtFaqsr3K10.1128/AAC.04954-14258458604468677
– reference: Nair, G. et al. in 8th IAS Conference on Pathogenesis Treatment & Prevention. Abstract # TUACO206LB.
– reference: ChapmanEHKurecASDaveyFRCell volumes of normal and malignant mononuclear cellsJ. Clin. Pathol.198134108310901:STN:280:DyaL38%2Fns1Wrtw%3D%3D10.1136/jcp.34.10.10836975780494369
– reference: UNAIDS. 90-90-0: An Ambitious Treatment Target to Help End the AIDS Epidemic. Report No. UNAIDS/JC2684, 40 (UNAIDS, Geneva, CH, 2014).
– reference: BirkusGIntracellular activation of tenofovir alafenamide and the effect of viral and host protease inhibitorsAntimicrob. Agents Chemother.2016603163221:CAS:528:DC%2BC28XhtVCrs7nP10.1128/aac.01834-1526503655
– reference: BaumMMHighly synergistic drug combination prevents vaginal HIV infection in humanized miceSci. Rep.202010129952020NatSR..1012995B1:CAS:528:DC%2BB3cXhsFers7vP10.1038/s41598-020-69937-5327476827400648
– reference: Pons-FaudoaFPViral load reduction in SHIV-positive nonhuman primates via long-acting subcutaneous tenofovir alafenamide fumarate release from a nanofluidic implantPharmaceutics202010.3390/pharmaceutics12100981330807767590004
– reference: NorrisJLCaprioliRMAnalysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical researchChem. Rev.2013113230923421:CAS:528:DC%2BC3sXit1Ght7w%3D10.1021/cr3004295233941643624074
– reference: SuJTA Subcutaneous implant of tenofovir alafenamide fumarate causes local inflammation and tissue necrosis in rabbits and macaquesAntimicrob. Agents Chemother.201910.1128/AAC.01893-19315270246879226
– reference: GallayPAProtection efficacy of C5A against vaginal and rectal HIV challenges in humanized miceOpen Virol. J.2018121131:CAS:528:DC%2BC1MXktlyqsrc%3D10.2174/1874357901812010001295412735842390
– reference: GunawardanaMMultispecies, in vivo evaluation of subdermal implants delivering tenofovir alafenamide: Of mice, dogs and sheepAIDS Res. Hum. Retrovir.201834107107
– reference: GorbachPMOrder of orifices: Sequence of condom use and ejaculation by orifice during anal intercourse among women: implications for HIV transmissionJ. Acquir. Immune Defic. Syndr.20146742442910.1097/QAI.0000000000000314253567784217134
– reference: HendrixCWHIV antiretroviral pre-exposure prophylaxis: Development challenges and pipeline promiseClin. Pharmacol. Ther.20181041082109710.1002/cpt.122730199098
– reference: MarzinkeMACharacterization of HIV infection in cisgender men and transgender women who have sex with men receiving injectable cabotegravir for HIV prevention: HPTN 083J. Infect. Dis.202110.1093/infdis/jiab152337400578599849
– reference: RosenEPAnalysis of antiretrovirals in single hair strands for evaluation of drug adherence with infrared-matrix-assisted laser desorption electrospray ionization mass spectrometry imagingAnal. Chem.201688133613441:CAS:528:DC%2BC2MXitVGrsrfF10.1021/acs.analchem.5b0379426688545
– reference: AmicoKRMansoorLECorneliATorjesenKvan der StratenAAdherence support approaches in biomedical HIV prevention trials: Experiences, insights and future directions from four multisite prevention trialsAIDS Behav.2013172143215510.1007/s10461-013-0429-9234356973672509
– reference: SchlesingerEA Tunable, biodegradable, thin-film polymer device as a long-acting implant delivering tenofovir alafenamide fumarate for hiv pre-exposure prophylaxisPharm. Res.201633164916561:CAS:528:DC%2BC28Xkt1Wnurw%3D10.1007/s11095-016-1904-6269753574892981
– reference: ThompsonCGHeterogeneous antiretroviral drug distribution and HIV/SHIV detection in the gut of three speciesSci. Transl. Med.201910.1126/scitranslmed.aap8758313160098273920
– reference: DurhamSHChahineEBCabotegravir-rilpivirine: The first complete long-acting injectable regimen for the treatment of HIV-1 infectionAnn. Pharmacother.202110.1177/106002802199558633593093
– reference: ChuaCYXTranscutaneously refillable nanofluidic implant achieves sustained level of tenofovir diphosphate for HIV pre-exposure prophylaxisJ. Control. Release20182863153251:CAS:528:DC%2BC1cXhsVKqsrvN10.1016/j.jconrel.2018.08.010300922546345255
– reference: LiLJohnsonLMKroviSADemkovichZRvan der StratenAPerformance and stability of tenofovir alafenamide formulations within subcutaneous biodegradable implants for HIV Pre-exposure prophylaxis (PrEP)Pharmaceutics202010.3390/pharmaceutics12111057332719007760669
– reference: GengiahTNMoosaANaidooAMansoorLEAdherence challenges with drugs for pre-exposure prophylaxis to prevent HIV infectionInt. J. Clin. Pharm.20143670851:CAS:528:DC%2BC2cXptFarug%3D%3D10.1007/s11096-013-9861-124129582
– reference: VegasAJCombinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primatesNat. Biotechnol.2016343453521:CAS:528:DC%2BC28XhsFyjtbk%3D10.1038/nbt.3462268075274904301
– reference: UNAIDS. Prevailing against Pandemics by Putting People at the Centre—World AIDS Day Report 2020. Report No. UNAIDS/JC3007E, 92 (UNAIDS, Geneva, CH, 2020).
– reference: BirkusGActivation of 9-[(R)-2-[[(S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]-methoxy]propyl]adenine (GS-7340) and other tenofovir phosphonoamidate prodrugs by human proteasesMol. Pharmacol.200874921001:CAS:528:DC%2BD1cXot1aksLc%3D10.1124/mol.108.04552618430788
– reference: Kuo, S.- H. & Kuzma, P. Long Term Drug Delivery Devices with Polyurethane Based Polymers and their Manufacture. USA patent U.S. Patent 7,842,303 B2 (2010).
– reference: ChumbleyCWAbsolute quantitative MALDI imaging mass spectrometry: A case of rifampicin in liver tissuesAnal. Chem.201688239223981:CAS:528:DC%2BC28Xhtlymsr0%3D10.1021/acs.analchem.5b04409268146655080977
– reference: DuwalSSchütteCvon KleistMPharmacokinetics and pharmacodynamics of the reverse transcriptase inhibitor tenofovir and prophylactic efficacy against HIV-1 infectionPLoS ONE20127e403822012PLoSO...740382D1:CAS:528:DC%2BC38XhtVKrsrzJ10.1371/journal.pone.0040382228081483394807
– reference: ISO. ISO 10993-6: Biological Evaluation of Medical Devices—Part 6: Tests for Local Effects After Implantation. 29 (International Organization for Standardization, Geneva, Switzerland, 2016).
– reference: GrantRMPreexposure chemoprophylaxis for HIV prevention in men who have sex with menN. Engl. J. Med.2010363258725991:CAS:528:DC%2BC3MXit1ansg%3D%3D10.1056/NEJMoa1011205210912793079639
– reference: BirkusGCathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131Antimicrob. Agents Chemother.2007515435501:CAS:528:DC%2BD2sXhsVOqu70%3D10.1128/aac.00968-0617145787
– reference: RomanoJWTenofovir alafenamide for HIV prevention: Review of the proceedings from the gates foundation long-acting TAF product development meetingAIDS Res. Hum. Retroviruses2021374094201:CAS:528:DC%2BB3MXht1WrsLbL10.1089/aid.2021.0028339137608213003
– reference: Gengiah, T. et al. CAPRISA 018: A phase I/II trial to assess the safety, acceptability, tolerability and pharmacokinetics of a sustained-release tenofovir alafenamide sub-dermal implant for HIV prevention in women. BMJ Open, 12(1), e052880. https://doi.org/10.1136/bmjopen-2021-052880 (2022).
– reference: BamRAYantSRCihlarTTenofovir alafenamide is not a substrate for renal organic anion transporters (OATs) and does not exhibit OAT-dependent cytotoxicityAntivir. Ther.2014196876921:CAS:528:DC%2BC2MXisVOguro%3D10.3851/imp277024699134
– reference: SeneviratneHKHendrixCWFuchsEJBumpusNNMALDI mass spectrometry imaging reveals heterogeneous distribution of tenofovir and tenofovir diphosphate in colorectal tissue of subjects receiving a tenofovir-containing enemaJ. Pharmacol. Exp. Ther.201836740481:CAS:528:DC%2BC1cXitVegsLzF10.1124/jpet.118.250357300378136123665
– reference: GunawardanaMBaumMMSmithTJMossJAAn intravaginal ring for the sustained delivery of antibodiesJ. Pharm. Sci.2014103361136201:CAS:528:DC%2BC2cXhslOkurvL10.1002/jps.24154252311934206599
– reference: ChoopanyaKAntiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): A Randomised, double-blind, placebo-controlled phase 3 trialLancet20133812083209010.1016/S0140-6736(13)61127-723769234
– reference: GallayPAPrevention of vaginal and rectal HIV transmission by antiretroviral combinations in humanized micePLoS ONE201712e01843031:CAS:528:DC%2BC1cXotFCgu70%3D10.1371/journal.pone.0184303288809485589224
– reference: Abdool KarimQEffectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in womenScience2010329116811742010Sci...329.1168A1:CAS:528:DC%2BC3cXhtV2hsr%2FI10.1126/science.1193748206439153001187
– reference: UNAIDS. Global Factsheet 2017, <AIDSinfo.unaids.org> (2018).
– reference: Hendrix, C. W. in 2014 Conference on Retroviruses and Opportunistic Infections (CROI). Oral Abstract 61 (CROI, Alexandria, VA).
– reference: GunawardanaMPharmacokinetics of long-acting tenofovir alafenamide (GS-7340) subdermal implant for HIV prophylaxisAntimicrob. Agents Chemother.201559391339191:CAS:528:DC%2BC2MXhtFaru7nJ10.1128/AAC.00656-15258966884468692
– reference: BabusisDPhanTKLeeWAWatkinsWJRayASMechanism for effective lymphoid cell and tissue loading following oral administration of nucleotide prodrug GS-7340Mol. Pharmaceut.2013104594661:CAS:528:DC%2BC38Xpt1Ortbs%3D10.1021/mp3002045
– reference: MarcusJLPreexposure prophylaxis for HIV prevention in a large integrated health care system: Adherence, renal safety, and discontinuationJ. Acquir. Immune Defic. Syndr.20167354054610.1097/QAI.0000000000001129278517145424697
– reference: RayASFordyceMWHitchcockMJMTenofovir alafenamide: A novel prodrug of tenofovir for the treatment of human immunodeficiency virusAntiviral Res.201612563701:CAS:528:DC%2BC2MXitVSktLjN10.1016/j.antiviral.2015.11.00926640223
– reference: Hare, C. B. et al. in 2019 Conference on Retroviruses and Opportunistic Infections (CROI). Abstract Number 104 (CROI, Alexandria, VA).
– reference: SeneviratneHKHamlinANHeckCJSBumpusNNSpatial distribution profiles of emtricitabine, tenofovir, efavirenz, and rilpivirine in murine tissues following in vivo dosing correlate with their safety profiles in humansACS Pharmacol. Transl. Sci.202036556651:CAS:528:DC%2BB3cXnslehsLc%3D10.1021/acsptsci.0c0001532832868
– reference: LouissaintNASingle dose pharmacokinetics of oral tenofovir in plasma, peripheral blood mononuclear cells, colonic tissue, and vaginal tissueAIDS Res. Hum. Retroviruses201329144314501:CAS:528:DC%2BC3sXhs1ylsbbK10.1089/aid.2013.0044236003653809387
– reference: AndersonPLEmtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with menSci. Transl. Med.201241511:CAS:528:DC%2BC38XhsFOkurvI10.1126/scitranslmed.3004006
– reference: WardKWHardyLBKehlerJRAzzaranoLMSmithBRApparent absolute oral bioavailability in excess of 100% for a vitronectin receptor antagonist (SB-265123) in Rat. II. Studies implicating transporter-mediated intestinal secretionXenobiotica2004343673771:CAS:528:DC%2BD2cXjsF2jurY%3D10.1080/0049825042000205540a15268981
– reference: SimpsonSMDesign of a drug-eluting subcutaneous implant of the antiretroviral tenofovir alafenamide fumaratePharm. Res.202037831:CAS:528:DC%2BB3cXntFOqsb8%3D10.1007/s11095-020-2777-2322969517160069
– reference: GunawardanaMMultispecies evaluation of a long-acting tenofovir alafenamide subdermal implant for HIV prophylaxisFront. Pharmacol.2020115693731:CAS:528:DC%2BB3MXns1yqu7s%3D10.3389/fphar.2020.569373335369047849190
– reference: GesselMMNorrisJLCaprioliRMMALDI imaging mass spectrometry: Spatial molecular analysis to enable a new age of discoveryJ. Proteomics201410771821:CAS:528:DC%2BC2cXmtVWrtLc%3D10.1016/j.jprot.2014.03.02124686089
– reference: LandovitzRJCabotegravir for HIV prevention in cisgender men and transgender womenN. Engl. J. Med.20213855956081:CAS:528:DC%2BB3MXhvVeqt7nI10.1056/NEJMoa2101016343799228448593
– reference: DentonPWSystemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT micePLoS ONE20105e88292010PLoSO...5.8829D1:CAS:528:DC%2BC3cXht1emtrk%3D10.1371/journal.pone.0008829200986232809117
– reference: ThompsonCGMass spectrometry imaging reveals heterogeneous efavirenz distribution within putative HIV reservoirsAntimicrob. Agents Chemother.201559294429481:CAS:528:DC%2BC2MXms12rtbo%3D10.1128/aac.04952-14257335024394831
– reference: BaetenJMAntiretroviral prophylaxis for HIV prevention in heterosexual men and womenN. Engl. J. Med.20123673994101:CAS:528:DC%2BC38XhtlSltrbK10.1056/NEJMoa1108524227840373770474
– reference: PrathipatiPKMandalSPonGVivekanandanRDestacheCJPharmacokinetic and tissue distribution profile of long acting tenofovir alafenamide and elvitegravir loaded nanoparticles in humanized mice modelPharm. Res.201734274927551:CAS:528:DC%2BC2sXhsVyqsrjE10.1007/s11095-017-2255-7289051735738272
– reference: WardKWPreclinical pharmacokinetics and interspecies scaling of a novel vitronectin receptor antagonistDrug. Metab. Dispos.199927123212411:CAS:528:DyaK1MXntFShtro%3D10534306
– reference: KastelloriziosMTipnisNBurgessDJLambrisJDEkdahlKNRicklinDNilssonBImmune Responses to Biosurfaces: Mechanisms and Therapeutic InterventionsAdvances in Experimental Medicine and Biology2015Springer93108
– reference: ThigpenMCAntiretroviral preexposure prophylaxis for heterosexual HIV transmission in BotswanaN. Engl. J. Med.20123674234341:CAS:528:DC%2BC38XhtlSltrbE10.1056/NEJMoa111071122784038
– reference: HendrixCWMTN-001: Randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartmentsPLoS ONE20138e550132013PLoSO...855013H1:CAS:528:DC%2BC3sXis1art70%3D10.1371/journal.pone.0055013233830373559346
– reference: MuchombaFMGearingRESimoniJMEl-BasselNState of the science of adherence in pre-exposure prophylaxis and microbicide trialsJAIDS2012614904981:CAS:528:DC%2BC38Xhs1entb3K10.1097/QAI.0b013e31826f996222932322
– reference: JohnsonLMCharacterization of a reservoir-style implant for sustained release of tenofovir alafenamide (TAF) for HIV pre-exposure prophylaxis (PrEP)Pharmaceutics20194E3151:CAS:528:DC%2BB3cXjslentbo%3D10.3390/pharmaceutics11070315
– reference: WardKWAzzaranoLMEvansCASmithBRApparent absolute oral bioavailability in excess of 100% for a vitronectin receptor antagonist (SB-265123) in Rat. I. Investigation of potential experimental and mechanistic explanationsXenobiotica20043435336610.1080/004982504200020554015268980
– reference: HummertPParsonsTLEnsignLMHoangTMarzinkeMAValidation and implementation of liquid chromatographic-mass spectrometric (LC-MS) methods for the quantification of tenofovir prodrugsJ. Pharm. Biomed. Anal.20181522482561:CAS:528:DC%2BC1cXis1aqt7w%3D10.1016/j.jpba.2018.02.011294330975835418
– reference: KellerMJA phase 1 randomized placebo-controlled safety and pharmacokinetic trial of a tenofovir disoproxil fumarate vaginal ringAIDS2016307437511:CAS:528:DC%2BC28XjsFGmurc%3D10.1097/qad.000000000000097926605514
– reference: SpreenWRMargolisDAPottageJCLong-acting Injectable antiretrovirals for HIV treatment and preventionCurr. Opin. HIV AIDS201385655711:CAS:528:DC%2BC3sXhs1WltrfF10.1097/coh.0000000000000002241008773815009
– volume: 4
  start-page: E315
  year: 2019
  ident: 11020_CR35
  publication-title: Pharmaceutics
  doi: 10.3390/pharmaceutics11070315
– ident: 11020_CR2
– volume: 51
  start-page: 543
  year: 2007
  ident: 11020_CR51
  publication-title: Antimicrob. Agents Chemother.
  doi: 10.1128/aac.00968-06
– volume: 363
  start-page: 2587
  year: 2010
  ident: 11020_CR14
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1011205
– volume: 286
  start-page: 315
  year: 2018
  ident: 11020_CR34
  publication-title: J. Control. Release
  doi: 10.1016/j.jconrel.2018.08.010
– volume: 37
  start-page: 83
  year: 2020
  ident: 11020_CR37
  publication-title: Pharm. Res.
  doi: 10.1007/s11095-020-2777-2
– volume: 107
  start-page: 71
  year: 2014
  ident: 11020_CR49
  publication-title: J. Proteomics
  doi: 10.1016/j.jprot.2014.03.021
– volume: 22
  start-page: 27
  year: 1984
  ident: 11020_CR59
  publication-title: Adv. Enzyme Regul.
  doi: 10.1016/0065-2571(84)90007-4
– year: 2020
  ident: 11020_CR61
  publication-title: Pharmaceutics
  doi: 10.3390/pharmaceutics12111057
– volume: 27
  start-page: 1232
  year: 1999
  ident: 11020_CR65
  publication-title: Drug. Metab. Dispos.
– year: 2020
  ident: 11020_CR41
  publication-title: Antimicrob. Agents Chemother.
  doi: 10.1128/aac.00930-20
– volume: 30
  start-page: 743
  year: 2016
  ident: 11020_CR12
  publication-title: AIDS
  doi: 10.1097/qad.0000000000000979
– volume: 34
  start-page: 353
  year: 2004
  ident: 11020_CR66
  publication-title: Xenobiotica
  doi: 10.1080/0049825042000205540
– volume: 34
  start-page: 367
  year: 2004
  ident: 11020_CR67
  publication-title: Xenobiotica
  doi: 10.1080/0049825042000205540a
– volume: 8
  start-page: 565
  year: 2013
  ident: 11020_CR26
  publication-title: Curr. Opin. HIV AIDS
  doi: 10.1097/coh.0000000000000002
– volume: 59
  start-page: 3761
  year: 2015
  ident: 11020_CR10
  publication-title: Antimicrob. Agents Chemother.
  doi: 10.1128/AAC.04954-14
– volume: 367
  start-page: 399
  year: 2012
  ident: 11020_CR15
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1108524
– volume: 61
  start-page: 490
  year: 2012
  ident: 11020_CR22
  publication-title: JAIDS
  doi: 10.1097/QAI.0b013e31826f9962
– volume: 104
  start-page: 1082
  year: 2018
  ident: 11020_CR7
  publication-title: Clin. Pharmacol. Ther.
  doi: 10.1002/cpt.1227
– volume: 12
  start-page: 1
  year: 2018
  ident: 11020_CR57
  publication-title: Open Virol. J.
  doi: 10.2174/1874357901812010001
– volume: 19
  start-page: 687
  year: 2014
  ident: 11020_CR68
  publication-title: Antivir. Ther.
  doi: 10.3851/imp2770
– volume: 88
  start-page: 1336
  year: 2016
  ident: 11020_CR71
  publication-title: Anal. Chem.
  doi: 10.1021/acs.analchem.5b03794
– volume: 381
  start-page: 2083
  year: 2013
  ident: 11020_CR17
  publication-title: Lancet
  doi: 10.1016/S0140-6736(13)61127-7
– ident: 11020_CR80
– volume: 59
  start-page: 2944
  year: 2015
  ident: 11020_CR70
  publication-title: Antimicrob. Agents Chemother.
  doi: 10.1128/aac.04952-14
– volume: 387
  start-page: 53
  year: 2016
  ident: 11020_CR20
  publication-title: Lancet
  doi: 10.1016/s0140-6736(15)00056-2
– ident: 11020_CR1
– volume: 367
  start-page: 40
  year: 2018
  ident: 11020_CR72
  publication-title: J. Pharmacol. Exp. Ther.
  doi: 10.1124/jpet.118.250357
– volume: 52
  start-page: 3818
  year: 2013
  ident: 11020_CR47
  publication-title: Biochemistry
  doi: 10.1021/bi301519p
– volume: 56
  start-page: 103
  year: 2012
  ident: 11020_CR8
  publication-title: Antimicrob. Agents Chemother.
  doi: 10.1128/AAC.00597-11
– volume: 59
  start-page: 3913
  year: 2015
  ident: 11020_CR31
  publication-title: Antimicrob. Agents Chemother.
  doi: 10.1128/AAC.00656-15
– volume: 74
  start-page: 92
  year: 2008
  ident: 11020_CR52
  publication-title: Mol. Pharmacol.
  doi: 10.1124/mol.108.045526
– volume: 60
  start-page: 316
  year: 2016
  ident: 11020_CR53
  publication-title: Antimicrob. Agents Chemother.
  doi: 10.1128/aac.01834-15
– ident: 11020_CR79
– volume: 37
  start-page: 369
  year: 2010
  ident: 11020_CR4
  publication-title: Sex. Transm. Dis.
  doi: 10.1097/OLQ.0b013e3181cbf77d
– volume: 103
  start-page: 3611
  year: 2014
  ident: 11020_CR78
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.24154
– volume: 34
  start-page: 359
  year: 2018
  ident: 11020_CR38
  publication-title: AIDS Res. Hum. Retrovir.
– volume: 373
  start-page: 2237
  year: 2015
  ident: 11020_CR18
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1506273
– year: 2020
  ident: 11020_CR62
  publication-title: Pharmaceutics
  doi: 10.3390/pharmaceutics12100981
– volume: 3
  start-page: 655
  year: 2020
  ident: 11020_CR74
  publication-title: ACS Pharmacol. Transl. Sci.
  doi: 10.1021/acsptsci.0c00015
– volume: 152
  start-page: 248
  year: 2018
  ident: 11020_CR81
  publication-title: J. Pharm. Biomed. Anal.
  doi: 10.1016/j.jpba.2018.02.011
– volume: 125
  start-page: 63
  year: 2016
  ident: 11020_CR43
  publication-title: Antiviral Res.
  doi: 10.1016/j.antiviral.2015.11.009
– volume: 385
  start-page: 595
  year: 2021
  ident: 11020_CR28
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa2101016
– volume: 8
  start-page: e55013
  year: 2013
  ident: 11020_CR9
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0055013
– volume: 5
  start-page: e8829
  year: 2010
  ident: 11020_CR54
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0008829
– volume: 88
  start-page: 2392
  year: 2016
  ident: 11020_CR50
  publication-title: Anal. Chem.
  doi: 10.1021/acs.analchem.5b04409
– volume: 34
  start-page: 345
  year: 2016
  ident: 11020_CR76
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.3462
– ident: 11020_CR11
– volume: 37
  start-page: 409
  year: 2021
  ident: 11020_CR40
  publication-title: AIDS Res. Hum. Retroviruses
  doi: 10.1089/aid.2021.0028
– volume: 34
  start-page: 2749
  year: 2017
  ident: 11020_CR45
  publication-title: Pharm. Res.
  doi: 10.1007/s11095-017-2255-7
– year: 2021
  ident: 11020_CR29
  publication-title: J. Infect. Dis.
  doi: 10.1093/infdis/jiab152
– year: 2019
  ident: 11020_CR73
  publication-title: Sci. Transl. Med.
  doi: 10.1126/scitranslmed.aap8758
– ident: 11020_CR25
– volume: 113
  start-page: 2309
  year: 2013
  ident: 11020_CR48
  publication-title: Chem. Rev.
  doi: 10.1021/cr3004295
– volume: 20
  start-page: 268
  year: 2012
  ident: 11020_CR55
  publication-title: Trends Microbiol.
  doi: 10.1016/j.tim.2012.03.007
– volume: 10
  start-page: 459
  year: 2013
  ident: 11020_CR60
  publication-title: Mol. Pharmaceut.
  doi: 10.1021/mp3002045
– volume: 4
  start-page: 151
  year: 2012
  ident: 11020_CR64
  publication-title: Sci. Transl. Med.
  doi: 10.1126/scitranslmed.3004006
– ident: 11020_CR21
– start-page: 93
  volume-title: Advances in Experimental Medicine and Biology
  year: 2015
  ident: 11020_CR75
– volume: 329
  start-page: 1168
  year: 2010
  ident: 11020_CR13
  publication-title: Science
  doi: 10.1126/science.1193748
– year: 2021
  ident: 11020_CR30
  publication-title: Ann. Pharmacother.
  doi: 10.1177/1060028021995586
– volume: 19
  start-page: 1338
  year: 2015
  ident: 11020_CR6
  publication-title: AIDS Behav.
  doi: 10.1007/s10461-015-0997-y
– volume: 11
  start-page: 569373
  year: 2020
  ident: 11020_CR32
  publication-title: Front. Pharmacol.
  doi: 10.3389/fphar.2020.569373
– volume: 34
  start-page: 107
  year: 2018
  ident: 11020_CR39
  publication-title: AIDS Res. Hum. Retrovir.
– volume: 33
  start-page: 1649
  year: 2016
  ident: 11020_CR33
  publication-title: Pharm. Res.
  doi: 10.1007/s11095-016-1904-6
– ident: 11020_CR3
– volume: 36
  start-page: 70
  year: 2014
  ident: 11020_CR24
  publication-title: Int. J. Clin. Pharm.
  doi: 10.1007/s11096-013-9861-1
– volume: 12
  start-page: e0184303
  year: 2017
  ident: 11020_CR56
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0184303
– volume: 34
  start-page: 1083
  year: 1981
  ident: 11020_CR42
  publication-title: J. Clin. Pathol.
  doi: 10.1136/jcp.34.10.1083
– volume: 67
  start-page: 424
  year: 2014
  ident: 11020_CR5
  publication-title: J. Acquir. Immune Defic. Syndr.
  doi: 10.1097/QAI.0000000000000314
– volume: 20
  start-page: 323
  year: 2014
  ident: 11020_CR27
  publication-title: Nat. Med.
  doi: 10.1038/nm0414-323
– ident: 11020_CR77
– volume: 17
  start-page: 2143
  year: 2013
  ident: 11020_CR23
  publication-title: AIDS Behav.
  doi: 10.1007/s10461-013-0429-9
– volume: 73
  start-page: 540
  year: 2016
  ident: 11020_CR19
  publication-title: J. Acquir. Immune Defic. Syndr.
  doi: 10.1097/QAI.0000000000001129
– volume: 7
  start-page: e40382
  year: 2012
  ident: 11020_CR44
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0040382
– year: 2019
  ident: 11020_CR36
  publication-title: Antimicrob. Agents Chemother.
  doi: 10.1128/AAC.01893-19
– ident: 11020_CR63
  doi: 10.1136/bmjopen-2021-052880
– volume: 23
  start-page: 695
  year: 2003
  ident: 11020_CR69
  publication-title: Pharmacotherapy
  doi: 10.1592/phco.23.6.695.32189
– volume: 29
  start-page: 1443
  year: 2013
  ident: 11020_CR46
  publication-title: AIDS Res. Hum. Retroviruses
  doi: 10.1089/aid.2013.0044
– volume: 367
  start-page: 423
  year: 2012
  ident: 11020_CR16
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1110711
– volume: 10
  start-page: 12995
  year: 2020
  ident: 11020_CR58
  publication-title: Sci. Rep.
  doi: 10.1038/s41598-020-69937-5
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Snippet Global efforts aimed at preventing human immunodeficiency virus type one (HIV-1) infection in vulnerable populations appear to be stalling, limiting our...
Abstract Global efforts aimed at preventing human immunodeficiency virus type one (HIV-1) infection in vulnerable populations appear to be stalling, limiting...
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SubjectTerms 631/154/152
692/308/153
Adenine
Alanine - therapeutic use
Animal models
Animals
Anti-HIV Agents
Antiretroviral drugs
At risk populations
Dosage
Drug dosages
Female
HIV
HIV Infections - drug therapy
HIV Infections - prevention & control
Human immunodeficiency virus
Humanities and Social Sciences
Mass spectrometry
Mass spectroscopy
Metabolites
Mice
multidisciplinary
Pharmacokinetics
Pharmacology
Prophylaxis
Science
Science (multidisciplinary)
Spatial distribution
Tenofovir
Tenofovir - analogs & derivatives
Tenofovir - therapeutic use
Transplants & implants
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Title Fundamental aspects of long-acting tenofovir alafenamide delivery from subdermal implants for HIV prophylaxis
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