Tenofovir-Diphosphate in Dried Blood Spots vs Tenofovir in Urine/Plasma for Oral Preexposure Prophylaxis Adherence Monitoring

Abstract Background Tenofovir-diphosphate (TFV-DP) measured in dried blood spots (DBS) and tenofovir (TFV) measured in urine/plasma have been used to measure TFV-based oral pre-exposure prophylaxis (PrEP) adherence. However, there are limited data comparing these 3 metrics and their appropriate use...

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Veröffentlicht in:Open Forum Infectious Diseases 2022-08, Vol.9 (8), p.ofac405
Hauptverfasser: Niu, Xin, Kubiak, Rachel W, Siriprakaisil, Oraphan, Klinbuyaem, Virat, Sukrakanchana, Pra ornsuda, Cressey, Ratchada, Okochi, Hideaki, Gandhi, Monica, Cressey, Tim R, Drain, Paul K
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container_title Open Forum Infectious Diseases
container_volume 9
creator Niu, Xin
Kubiak, Rachel W
Siriprakaisil, Oraphan
Klinbuyaem, Virat
Sukrakanchana, Pra ornsuda
Cressey, Ratchada
Okochi, Hideaki
Gandhi, Monica
Cressey, Tim R
Drain, Paul K
description Abstract Background Tenofovir-diphosphate (TFV-DP) measured in dried blood spots (DBS) and tenofovir (TFV) measured in urine/plasma have been used to measure TFV-based oral pre-exposure prophylaxis (PrEP) adherence. However, there are limited data comparing these 3 metrics and their appropriate use for PrEP adherence monitoring. Methods We collected DBS, urine, and plasma samples from HIV-negative adults randomized to a low (2 doses/week), moderate (4 doses/week), or perfect (7 doses/week) adherence group (via directly observed therapy) of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for 6 weeks, followed by a 4-week washout phase. Drug concentrations were measured using liquid chromatography tandem mass spectrometry. Linear mixed-effects modeling was used to examine associations between drug concentrations and dosing time. Results Among 28 participants, the median age was 33 years, and 12 (43%) were female. At steady state, 25th percentile TFV-DP concentrations were 466, 779, and 1375 fmol/3 mm punch in the low, moderate, and perfect adherence group, respectively. Correlation was stronger between quantifiable TFV-DP and plasma TFV (r = 0.65; P 
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However, there are limited data comparing these 3 metrics and their appropriate use for PrEP adherence monitoring. Methods We collected DBS, urine, and plasma samples from HIV-negative adults randomized to a low (2 doses/week), moderate (4 doses/week), or perfect (7 doses/week) adherence group (via directly observed therapy) of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for 6 weeks, followed by a 4-week washout phase. Drug concentrations were measured using liquid chromatography tandem mass spectrometry. Linear mixed-effects modeling was used to examine associations between drug concentrations and dosing time. Results Among 28 participants, the median age was 33 years, and 12 (43%) were female. At steady state, 25th percentile TFV-DP concentrations were 466, 779, and 1375 fmol/3 mm punch in the low, moderate, and perfect adherence group, respectively. Correlation was stronger between quantifiable TFV-DP and plasma TFV (r = 0.65; P &lt; .01) than between TFV-DP and urine TFV (r = 0.50; P &lt; .01). Among all participants, each additional week of cumulative dosing on average led to a mean increase of 158 fmol/3 mm punch (P &lt; .001) in TFV-DP during the dosing phase. Each additional day after the last dose was associated with 43 fmol/3 mm punch lower TFV-DP (P = .07). Conclusions TFV-DP levels in DBS provide valuable insight into both dosing recency and cumulative doses from variable adherence patterns. Our observed benchmark TFV-DP concentrations were slightly higher than prior predicted estimates based on convenience samples.</description><identifier>ISSN: 2328-8957</identifier><identifier>EISSN: 2328-8957</identifier><identifier>DOI: 10.1093/ofid/ofac405</identifier><identifier>PMID: 36004315</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Analysis ; Emtricitabine ; Liquid chromatography ; Major ; Mass spectrometry ; Patient compliance ; Tenofovir</subject><ispartof>Open Forum Infectious Diseases, 2022-08, Vol.9 (8), p.ofac405</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</rights><rights>COPYRIGHT 2022 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-b0825c6514bb7fd7519c4e03dc56c7f1e53b3928cbd34431a4b8068a05e8371c3</citedby><cites>FETCH-LOGICAL-c483t-b0825c6514bb7fd7519c4e03dc56c7f1e53b3928cbd34431a4b8068a05e8371c3</cites><orcidid>0000-0002-7025-1994 ; 0000-0002-9569-4097</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394764/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394764/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,1605,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36004315$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Niu, Xin</creatorcontrib><creatorcontrib>Kubiak, Rachel W</creatorcontrib><creatorcontrib>Siriprakaisil, Oraphan</creatorcontrib><creatorcontrib>Klinbuyaem, Virat</creatorcontrib><creatorcontrib>Sukrakanchana, Pra ornsuda</creatorcontrib><creatorcontrib>Cressey, Ratchada</creatorcontrib><creatorcontrib>Okochi, Hideaki</creatorcontrib><creatorcontrib>Gandhi, Monica</creatorcontrib><creatorcontrib>Cressey, Tim R</creatorcontrib><creatorcontrib>Drain, Paul K</creatorcontrib><title>Tenofovir-Diphosphate in Dried Blood Spots vs Tenofovir in Urine/Plasma for Oral Preexposure Prophylaxis Adherence Monitoring</title><title>Open Forum Infectious Diseases</title><addtitle>Open Forum Infect Dis</addtitle><description>Abstract Background Tenofovir-diphosphate (TFV-DP) measured in dried blood spots (DBS) and tenofovir (TFV) measured in urine/plasma have been used to measure TFV-based oral pre-exposure prophylaxis (PrEP) adherence. However, there are limited data comparing these 3 metrics and their appropriate use for PrEP adherence monitoring. Methods We collected DBS, urine, and plasma samples from HIV-negative adults randomized to a low (2 doses/week), moderate (4 doses/week), or perfect (7 doses/week) adherence group (via directly observed therapy) of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for 6 weeks, followed by a 4-week washout phase. Drug concentrations were measured using liquid chromatography tandem mass spectrometry. Linear mixed-effects modeling was used to examine associations between drug concentrations and dosing time. Results Among 28 participants, the median age was 33 years, and 12 (43%) were female. At steady state, 25th percentile TFV-DP concentrations were 466, 779, and 1375 fmol/3 mm punch in the low, moderate, and perfect adherence group, respectively. Correlation was stronger between quantifiable TFV-DP and plasma TFV (r = 0.65; P &lt; .01) than between TFV-DP and urine TFV (r = 0.50; P &lt; .01). Among all participants, each additional week of cumulative dosing on average led to a mean increase of 158 fmol/3 mm punch (P &lt; .001) in TFV-DP during the dosing phase. Each additional day after the last dose was associated with 43 fmol/3 mm punch lower TFV-DP (P = .07). Conclusions TFV-DP levels in DBS provide valuable insight into both dosing recency and cumulative doses from variable adherence patterns. Our observed benchmark TFV-DP concentrations were slightly higher than prior predicted estimates based on convenience samples.</description><subject>Analysis</subject><subject>Emtricitabine</subject><subject>Liquid chromatography</subject><subject>Major</subject><subject>Mass spectrometry</subject><subject>Patient compliance</subject><subject>Tenofovir</subject><issn>2328-8957</issn><issn>2328-8957</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><recordid>eNp9kUFv1DAQhSMEolXpjTPyDQ6ktWM7Ti5IS0sBqaiVaM-W40w2Rokn2MmqPfDf69Uuq3JBluzR-HtPM3pZ9pbRM0Zrfo6da9NlrKDyRXZc8KLKq1qql8_qo-w0xl-UUsaopKp-nR3xklLBmTzO_tyBxw43LuSXbuoxTr2ZgThPLoODlnweEFvyc8I5kk0kB3pL3Afn4fx2MHE0pMNAboIZyG0AeJgwLgFSjVP_OJgHF8mq7SGAt0B-oHczJvH6TfaqM0OE0_17kt1ffbm7-JZf33z9frG6zq2o-Jw3tCqkLSUTTaO6VklWWwGUt1aWVnUMJG94XVS2ablIexnRVLSsDJVQccUsP8k-7XynpRmhteDnNKqeghtNeNRonP73x7ter3Gja14LVYpk8GFvEPD3AnHWo4sWhsF4wCXqQtFSsVpxmtCzHbo2A2jnO0yONp0WRmfRQ-dSf6VUyYQqZJEEH3cCGzDGAN1hLkb1NmW9TVnvU074u-e7HOC_mSbg_Q7AZfq_1RPQRLQf</recordid><startdate>20220801</startdate><enddate>20220801</enddate><creator>Niu, Xin</creator><creator>Kubiak, Rachel W</creator><creator>Siriprakaisil, Oraphan</creator><creator>Klinbuyaem, Virat</creator><creator>Sukrakanchana, Pra ornsuda</creator><creator>Cressey, Ratchada</creator><creator>Okochi, Hideaki</creator><creator>Gandhi, Monica</creator><creator>Cressey, Tim R</creator><creator>Drain, Paul K</creator><general>Oxford University Press</general><scope>TOX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IAO</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7025-1994</orcidid><orcidid>https://orcid.org/0000-0002-9569-4097</orcidid></search><sort><creationdate>20220801</creationdate><title>Tenofovir-Diphosphate in Dried Blood Spots vs Tenofovir in Urine/Plasma for Oral Preexposure Prophylaxis Adherence Monitoring</title><author>Niu, Xin ; Kubiak, Rachel W ; Siriprakaisil, Oraphan ; Klinbuyaem, Virat ; Sukrakanchana, Pra ornsuda ; Cressey, Ratchada ; Okochi, Hideaki ; Gandhi, Monica ; Cressey, Tim R ; Drain, Paul K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-b0825c6514bb7fd7519c4e03dc56c7f1e53b3928cbd34431a4b8068a05e8371c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Analysis</topic><topic>Emtricitabine</topic><topic>Liquid chromatography</topic><topic>Major</topic><topic>Mass spectrometry</topic><topic>Patient compliance</topic><topic>Tenofovir</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Niu, Xin</creatorcontrib><creatorcontrib>Kubiak, Rachel W</creatorcontrib><creatorcontrib>Siriprakaisil, Oraphan</creatorcontrib><creatorcontrib>Klinbuyaem, Virat</creatorcontrib><creatorcontrib>Sukrakanchana, Pra ornsuda</creatorcontrib><creatorcontrib>Cressey, Ratchada</creatorcontrib><creatorcontrib>Okochi, Hideaki</creatorcontrib><creatorcontrib>Gandhi, Monica</creatorcontrib><creatorcontrib>Cressey, Tim R</creatorcontrib><creatorcontrib>Drain, Paul K</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale Academic OneFile</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Open Forum Infectious Diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Niu, Xin</au><au>Kubiak, Rachel W</au><au>Siriprakaisil, Oraphan</au><au>Klinbuyaem, Virat</au><au>Sukrakanchana, Pra ornsuda</au><au>Cressey, Ratchada</au><au>Okochi, Hideaki</au><au>Gandhi, Monica</au><au>Cressey, Tim R</au><au>Drain, Paul K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tenofovir-Diphosphate in Dried Blood Spots vs Tenofovir in Urine/Plasma for Oral Preexposure Prophylaxis Adherence Monitoring</atitle><jtitle>Open Forum Infectious Diseases</jtitle><addtitle>Open Forum Infect Dis</addtitle><date>2022-08-01</date><risdate>2022</risdate><volume>9</volume><issue>8</issue><spage>ofac405</spage><pages>ofac405-</pages><issn>2328-8957</issn><eissn>2328-8957</eissn><abstract>Abstract Background Tenofovir-diphosphate (TFV-DP) measured in dried blood spots (DBS) and tenofovir (TFV) measured in urine/plasma have been used to measure TFV-based oral pre-exposure prophylaxis (PrEP) adherence. However, there are limited data comparing these 3 metrics and their appropriate use for PrEP adherence monitoring. Methods We collected DBS, urine, and plasma samples from HIV-negative adults randomized to a low (2 doses/week), moderate (4 doses/week), or perfect (7 doses/week) adherence group (via directly observed therapy) of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for 6 weeks, followed by a 4-week washout phase. Drug concentrations were measured using liquid chromatography tandem mass spectrometry. Linear mixed-effects modeling was used to examine associations between drug concentrations and dosing time. Results Among 28 participants, the median age was 33 years, and 12 (43%) were female. At steady state, 25th percentile TFV-DP concentrations were 466, 779, and 1375 fmol/3 mm punch in the low, moderate, and perfect adherence group, respectively. Correlation was stronger between quantifiable TFV-DP and plasma TFV (r = 0.65; P &lt; .01) than between TFV-DP and urine TFV (r = 0.50; P &lt; .01). Among all participants, each additional week of cumulative dosing on average led to a mean increase of 158 fmol/3 mm punch (P &lt; .001) in TFV-DP during the dosing phase. Each additional day after the last dose was associated with 43 fmol/3 mm punch lower TFV-DP (P = .07). Conclusions TFV-DP levels in DBS provide valuable insight into both dosing recency and cumulative doses from variable adherence patterns. Our observed benchmark TFV-DP concentrations were slightly higher than prior predicted estimates based on convenience samples.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>36004315</pmid><doi>10.1093/ofid/ofac405</doi><orcidid>https://orcid.org/0000-0002-7025-1994</orcidid><orcidid>https://orcid.org/0000-0002-9569-4097</orcidid><oa>free_for_read</oa></addata></record>
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subjects Analysis
Emtricitabine
Liquid chromatography
Major
Mass spectrometry
Patient compliance
Tenofovir
title Tenofovir-Diphosphate in Dried Blood Spots vs Tenofovir in Urine/Plasma for Oral Preexposure Prophylaxis Adherence Monitoring
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