Emtricitabine seminal plasma and blood plasma population pharmacokinetics in HIV-infected men in the EVARIST ANRS-EP 49 study.
We aimed to describe blood plasma (BP) and seminal plasma (SP) pharmacokinetics of emtricitabine (FTC) in HIV-1-infected men, assess its penetration in the male genital tract, and evaluate its impact on seminal plasma HIV load (spVL) detection. Men from the EVARIST ANRS EP49 study receiving combined antiretroviral therapy with FTC and with suppressed BP viral load were included in the study. A total of 236 and 209 FTC BP and SP concentrations, respectively, were available. A population pharmacokinetic model was developed with Monolix 4.1.4. The impact of FTC seminal exposure on spVL detection was explored by receiver operating characteristic (ROC) curves and mixed-effects logistic regressions. FTC BP pharmacokinetics was described by a two-compartment model. The addition of an effect compartment with different input and output constants best described FTC SP pharmacokinetics. No covariates were found to explain the variability in SP. FTC exposures (area under the concentration-time curve from 0 to 24 h [AUC0-24]) were higher in SP than in BP (median AUC0-24, 38.04 and 12.95 mg · liter(-1) · h, respectively). The median (range) SP-to-BP AUC0-24 ratio was 2.91 (0.84 to 10.08). Less than 1% of FTC AUC0-24 ratios were lower than 1. The impact of FTC SP AUC0-24 or FTC SP-to-BP AUC0-24 ratio on spVL detection was not significant (P = 0.943 or 0.893, respectively). This is the first population model describing FTC pharmacokinetics simultaneously in both BP and SP. FTC distributes well in the male genital tract with higher FTC concentrations in SP than in BP. FTC seminal plasma exposures were considered efficient in the majority of men.
Université Paris Descartes, EA 08, Sorbonne Paris-Cité, Paris, France Unité de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, Paris, France elodie.valade@free.fr.
Elodie
E
Valade
Université Paris Descartes, EA 08, Sorbonne Paris-Cité, Paris, France Unité de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, Paris, France CIC-1419 INSERM, Cochin-Necker, Paris, France Service de Pharmacologie Clinique, Hôpital Cochin, AP-HP, Groupe Hospitalier Paris Centre, Paris, France.
Jean-Marc
JM
Tréluyer
Université Paris Descartes, EA 08, Sorbonne Paris-Cité, Paris, France Unité de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, Paris, France CIC-1419 INSERM, Cochin-Necker, Paris, France Service de Pharmacologie Clinique, Hôpital Cochin, AP-HP, Groupe Hospitalier Paris Centre, Paris, France.
Silvia M
SM
Illamola
Université Paris Descartes, EA 08, Sorbonne Paris-Cité, Paris, France Unité de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, Paris, France CIC-1419 INSERM, Cochin-Necker, Paris, France.
Naïm
N
Bouazza
Université Paris Descartes, EA 08, Sorbonne Paris-Cité, Paris, France Unité de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, Paris, France CIC-1419 INSERM, Cochin-Necker, Paris, France.
Frantz
F
Foissac
Université Paris Descartes, EA 08, Sorbonne Paris-Cité, Paris, France Unité de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, Paris, France.
Maïlys
M
De Sousa Mendes
Université Paris Descartes, EA 08, Sorbonne Paris-Cité, Paris, France Service de Pharmacologie Clinique, Hôpital Cochin, AP-HP, Groupe Hospitalier Paris Centre, Paris, France.
Gabrielle
G
Lui
Service de Diagnostic Biologique Automatisé, Hôpital Cochin, Hôpitaux Universitaires Paris Centre (HUPC), Assistance Publique des Hôpitaux de Paris (AP-HP), Paris, France.
Camille
C
Chenevier-Gobeaux
INSERM, UMR912 (SESSTIM), Marseille, France UMR_S912, IRD, Aix Marseille Université, Marseille, France ORS PACA, Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France.
Marie
M
Suzan-Monti
Université Paris Descartes, EA 7327, Sorbonne Paris-Cité, Paris, France Laboratoire de Virologie, Centre Hospitalier Universitaire Necker Enfants Malades, AP-HP, Paris, France.
Christine
C
Rouzioux
INSERM, UMR-S 943, Université Pierre et Marie Curie, Paris, France.
Lambert
L
Assoumou
Université Paris Descartes, EA 7327, Sorbonne Paris-Cité, Paris, France Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Centre Hospitalier Universitaire Hôtel-Dieu, AP-HP, Paris, France.
Jean-Paul
JP
Viard
Université Paris Descartes, EA 08, Sorbonne Paris-Cité, Paris, France Unité de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, Paris, France CIC-1419 INSERM, Cochin-Necker, Paris, France Service de Pharmacologie Clinique, Hôpital Cochin, AP-HP, Groupe Hospitalier Paris Centre, Paris, France.
Déborah
D
Hirt
Université Paris Descartes, EA 08, Sorbonne Paris-Cité, Paris, France Unité de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, Paris, France CIC-1419 INSERM, Cochin-Necker, Paris, France.
Saïk
S
Urien
Université Paris Descartes, EA 7327, Sorbonne Paris-Cité, Paris, France Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Centre Hospitalier Universitaire Hôtel-Dieu, AP-HP, Paris, France.
Jade
J
Ghosn
D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068679:Emtricitabine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism*; D012661:Semen / Q000378:metabolism*
D019380:Anti-HIV Agents; D000068679:Emtricitabine