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Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial

It is critical to assess adherence to pre-exposure prophylaxis (PrEP) in clinical trials. The relationship between pharmacokinetic measures of PrEP adherence and other adherence measures used in PrEP trials requires further characterization. Plasma, peripheral blood mononuclear cells (PBMCs), and ha...

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Autores principales: Baxi, Sanjiv M., Vittinghoff, Eric, Bacchetti, Peter, Huang, Yong, Chillag, Kata, Wiegand, Ryan, Anderson, Peter L., Grant, Robert, Greenblatt, Ruth M., Buchbinder, Susan, Gandhi, Monica, Liu, Albert Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760024/
https://www.ncbi.nlm.nih.gov/pubmed/29315307
http://dx.doi.org/10.1371/journal.pone.0190118
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author Baxi, Sanjiv M.
Vittinghoff, Eric
Bacchetti, Peter
Huang, Yong
Chillag, Kata
Wiegand, Ryan
Anderson, Peter L.
Grant, Robert
Greenblatt, Ruth M.
Buchbinder, Susan
Gandhi, Monica
Liu, Albert Y.
author_facet Baxi, Sanjiv M.
Vittinghoff, Eric
Bacchetti, Peter
Huang, Yong
Chillag, Kata
Wiegand, Ryan
Anderson, Peter L.
Grant, Robert
Greenblatt, Ruth M.
Buchbinder, Susan
Gandhi, Monica
Liu, Albert Y.
author_sort Baxi, Sanjiv M.
collection PubMed
description It is critical to assess adherence to pre-exposure prophylaxis (PrEP) in clinical trials. The relationship between pharmacokinetic measures of PrEP adherence and other adherence measures used in PrEP trials requires further characterization. Plasma, peripheral blood mononuclear cells (PBMCs), and hair samples were collected from 88 HIV-uninfected men who have sex with men in a placebo-controlled randomized PrEP trial; announced pill counts, medication electronic monitoring (MEMS), and self-report using visual analog scale (VAS) were also collected. Tenofovir (TFV or TFV-DP) in plasma, hair, and PBMCs were quantified. Proportions with drug detection, Spearman correlation coefficients, and univariate and multivariable regression models were used. Drug detection in plasma, PBMC, and hair samples was highly concordant with treatment arm assignment. TFV or TFV-DP levels were detected in most active-arm participants: 44/47 (94%) in plasma, 46/47 (98%) in hair, and 44/47 (94%) in PBMCs and in only 1/41 placebo arm participant. Correlation coefficients were r = 0.59 for plasma and PBMC, r = 0.34 for PBMC and hair and r = 0.36 for plasma and hair. MEMS and announced pill-counts were moderately correlated (r = 0.52) but less so with pharmacologic measures (range of r = 0.12 to 0.38). Self-reported adherence by visual analog scale demonstrated essentially no correlation with drug levels (r = 0.06 for hair, PBMC or plasma) and was a poor indicator of exposure to study product. Indices of drug exposure are important indicators in assessing adherence to PrEP; accounting for variability between measures may improve interpretation and use of adherence measures in future PrEP studies. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov NCT00131677
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spelling pubmed-57600242018-01-22 Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial Baxi, Sanjiv M. Vittinghoff, Eric Bacchetti, Peter Huang, Yong Chillag, Kata Wiegand, Ryan Anderson, Peter L. Grant, Robert Greenblatt, Ruth M. Buchbinder, Susan Gandhi, Monica Liu, Albert Y. PLoS One Research Article It is critical to assess adherence to pre-exposure prophylaxis (PrEP) in clinical trials. The relationship between pharmacokinetic measures of PrEP adherence and other adherence measures used in PrEP trials requires further characterization. Plasma, peripheral blood mononuclear cells (PBMCs), and hair samples were collected from 88 HIV-uninfected men who have sex with men in a placebo-controlled randomized PrEP trial; announced pill counts, medication electronic monitoring (MEMS), and self-report using visual analog scale (VAS) were also collected. Tenofovir (TFV or TFV-DP) in plasma, hair, and PBMCs were quantified. Proportions with drug detection, Spearman correlation coefficients, and univariate and multivariable regression models were used. Drug detection in plasma, PBMC, and hair samples was highly concordant with treatment arm assignment. TFV or TFV-DP levels were detected in most active-arm participants: 44/47 (94%) in plasma, 46/47 (98%) in hair, and 44/47 (94%) in PBMCs and in only 1/41 placebo arm participant. Correlation coefficients were r = 0.59 for plasma and PBMC, r = 0.34 for PBMC and hair and r = 0.36 for plasma and hair. MEMS and announced pill-counts were moderately correlated (r = 0.52) but less so with pharmacologic measures (range of r = 0.12 to 0.38). Self-reported adherence by visual analog scale demonstrated essentially no correlation with drug levels (r = 0.06 for hair, PBMC or plasma) and was a poor indicator of exposure to study product. Indices of drug exposure are important indicators in assessing adherence to PrEP; accounting for variability between measures may improve interpretation and use of adherence measures in future PrEP studies. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov NCT00131677 Public Library of Science 2018-01-09 /pmc/articles/PMC5760024/ /pubmed/29315307 http://dx.doi.org/10.1371/journal.pone.0190118 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Baxi, Sanjiv M.
Vittinghoff, Eric
Bacchetti, Peter
Huang, Yong
Chillag, Kata
Wiegand, Ryan
Anderson, Peter L.
Grant, Robert
Greenblatt, Ruth M.
Buchbinder, Susan
Gandhi, Monica
Liu, Albert Y.
Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial
title Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial
title_full Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial
title_fullStr Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial
title_full_unstemmed Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial
title_short Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial
title_sort comparing pharmacologic measures of tenofovir exposure in a u.s. pre-exposure prophylaxis randomized trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760024/
https://www.ncbi.nlm.nih.gov/pubmed/29315307
http://dx.doi.org/10.1371/journal.pone.0190118
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