Estimated pill intake with on-demand PrEP with oral TDF/FTC using TFV-DP concentration in dried blood spots in the ANRS IPERGAY trial.


Journal

The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617

Informations de publication

Date de publication:
15 09 2021
Historique:
received: 24 04 2021
accepted: 25 06 2021
pubmed: 20 7 2021
medline: 29 10 2021
entrez: 19 7 2021
Statut: ppublish

Résumé

Tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is a reliable pharmacokinetics biomarker of adherence to tenofovir disoproxil fumarate (TDF). We aimed to use DBSs to estimate pill intake among participants using on-demand pre-exposure prophylaxis (PrEP) and to identify predictive factors associated with higher TFV-DP concentrations. DBSs were collected at the last study visit of the open-label phase of the ANRS IPERGAY study, assessing on-demand oral TDF/emtricitabine for PrEP among MSM and transgender female participants. We quantified TFV-DP in DBSs centrally. We assessed correlation between pill count and TFV-DP concentration by Spearman correlation and explored associations between participant demographics, sexual behaviour and PrEP use during sexual intercourse (SI) with TFV-DP concentrations by univariate and multivariate logistic regression models. The median age of the 245 participants included in this study was 40 years, with a median body weight of 73 kg. Median (IQR) TFV-DP concentration reached 517 (128-868) fmol/punch, corresponding to an estimated intake of 8-12 tablets per month (2-3 doses per week). Only 39% of participants had a TFV-DP concentration above 700 fmol/punch. TFV-DP concentrations were moderately correlated with pill count (r: 0.59; P < 0.001). In multivariate analysis, only systematic use of PrEP during SI and more frequent episodes of SI in the past 4 weeks were significantly associated with higher TFV-DP levels [OR (95% CI): 11.30 (3.62-35.33) and 1.46 (1.19-1.79), respectively; P < 0.001]. Among participants using on-demand PrEP, estimated pill intake reached 8-12 tablets per month and was correlated with frequency and systematic use of PrEP for SI.

Sections du résumé

BACKGROUND
Tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is a reliable pharmacokinetics biomarker of adherence to tenofovir disoproxil fumarate (TDF). We aimed to use DBSs to estimate pill intake among participants using on-demand pre-exposure prophylaxis (PrEP) and to identify predictive factors associated with higher TFV-DP concentrations.
METHODS
DBSs were collected at the last study visit of the open-label phase of the ANRS IPERGAY study, assessing on-demand oral TDF/emtricitabine for PrEP among MSM and transgender female participants. We quantified TFV-DP in DBSs centrally. We assessed correlation between pill count and TFV-DP concentration by Spearman correlation and explored associations between participant demographics, sexual behaviour and PrEP use during sexual intercourse (SI) with TFV-DP concentrations by univariate and multivariate logistic regression models.
RESULTS
The median age of the 245 participants included in this study was 40 years, with a median body weight of 73 kg. Median (IQR) TFV-DP concentration reached 517 (128-868) fmol/punch, corresponding to an estimated intake of 8-12 tablets per month (2-3 doses per week). Only 39% of participants had a TFV-DP concentration above 700 fmol/punch. TFV-DP concentrations were moderately correlated with pill count (r: 0.59; P < 0.001). In multivariate analysis, only systematic use of PrEP during SI and more frequent episodes of SI in the past 4 weeks were significantly associated with higher TFV-DP levels [OR (95% CI): 11.30 (3.62-35.33) and 1.46 (1.19-1.79), respectively; P < 0.001].
CONCLUSIONS
Among participants using on-demand PrEP, estimated pill intake reached 8-12 tablets per month and was correlated with frequency and systematic use of PrEP for SI.

Identifiants

pubmed: 34278433
pii: 6323549
doi: 10.1093/jac/dkab253
doi:

Substances chimiques

Anti-HIV Agents 0
Organophosphates 0
tenofovir diphosphate 0
Tenofovir 99YXE507IL
Emtricitabine G70B4ETF4S
Adenine JAC85A2161

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2675-2680

Subventions

Organisme : Bill & Melinda Gates Foundation
Pays : United States

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Lauriane Goldwirt (L)

Assistance Publique des Hôpitaux de Paris, Saint-Louis Hospital, Department of Pharmacology, Université de Paris Diderot (Paris 7), INSERM UMRS976, France.

Rebecca Bauer (R)

Inserm SC10, Villejuif, France.

Geoffroy Liegeon (G)

Assistance Publique des Hôpitaux de Paris, Saint-Louis Hospital, Department of Infectious Diseases, Université de Paris Diderot (Paris 7), INSERM U941, Paris, France.

Isabelle Charreau (I)

Inserm SC10, Villejuif, France.

Constance Delaugerre (C)

Assistance Publique des Hôpitaux de Paris, Saint-Louis Hospital, Department of Virology, Université de Paris Diderot (Paris 7), INSERM U944, France.

Laurent Cotte (L)

Hospices Civils de Lyon, Croix-Rousse Hospital, Department of Infectious Diseases, INSERM U1052, Lyon, France.

Gilles Pialou (G)

Assistance Publique des Hôpitaux de Paris, Tenon Hospital, Department of Infectious Diseases, Sorbonne Université, UPMC Université, (Paris 6), France.

Eric Cua (E)

Hôpital de l'Archet, Department of Infectious Diseases, Nice University Hospital, France.

Aïcha Laghzal (A)

Assistance Publique des Hôpitaux de Paris, Saint-Louis Hospital, Department of Pharmacology, Université de Paris Diderot (Paris 7), INSERM UMRS976, France.

Lane Buschman (L)

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Peter L Anderson (PL)

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Samia Mourah (S)

Assistance Publique des Hôpitaux de Paris, Saint-Louis Hospital, Department of Pharmacology, Université de Paris Diderot (Paris 7), INSERM UMRS976, France.

Laurence Meyer (L)

Assistance Publique des Hôpitaux de Paris, Bicêtre Hospital, Université Paris-Saclay, UVSQ, Inserm, Le Kremlin-Bicêtre, France.

Jean-Michel Molina (JM)

Assistance Publique des Hôpitaux de Paris, Saint-Louis Hospital, Department of Infectious Diseases, Université de Paris Diderot (Paris 7), INSERM U941, Paris, France.

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Classifications MeSH