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J Antimicrob Chemother. 2017 Nov 1;72(11):3167-3171. doi: 10.1093/jac/dkx275.

Penetration and antiviral efficacy of total and unbound maraviroc, raltegravir and rilpivirine in both female and male genital fluids from HIV-positive patients receiving regimens containing these antiretrovirals.

Author information

1
AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Pharmaco-Toxicologie, Paris, France.
2
IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité and INSERM, Paris, France.
3
APHP, Hôpital Cochin, Centre d'Investigation Clinique Cochin Pasteur, Paris, France.
4
APHP, Hôpital Saint-Louis, Laboratoire de Virologie, INSERM U941, Paris, France.
5
APHP, Hôpital Cochin, Laboratoire de Biologie de la Reproduction, Paris, France.
6
Université Paris Descartes, Paris, France.
7
APHP, Hôpital Cochin, Service de Médecine Interne, Paris, France.
8
APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpitaux Universitaires Paris Centre site Hôtel Dieu, Paris, France.
9
Université Paris Descartes, EA 7327, Faculté de Médecine site Necker, Sorbonne Paris Cité, Paris, France.
10
APHP, Service des Maladies Infectieuses et Tropicales, Hôpital Necker Enfants Malades, Centre d'Infectiologie Necker-Pasteur, Paris, France.
11
Institut Pasteur, Centre Médical de l'Institut Pasteur, Centre d'Infectiologie Necker-Pasteur, Paris, France.

Abstract

Background:

Sub-optimal penetration of antiretroviral drugs in genital compartments might promote local HIV persistence and increase the risk of HIV transmission.

Objectives:

To describe the penetration of maraviroc, raltegravir, raltegravir glucuronide and rilpivirine in seminal plasma and cervico-vaginal secretions (CVS) and to assess local antiretroviral efficacy in HIV-1-positive patients.

Methods:

This was a prospective, multicentre study. Inclusion criteria were HIV-1 positive, age >18 years, receiving regimens containing maraviroc and/or raltegravir and/or rilpivirine for >1 month, and good self-reported adherence. Paired blood and genital samples were collected 12 h (raltegravir and maraviroc) or 24 h (rilpivirine) post-dose. These concentrations were determined (UPLC-MS/MS) in blood and seminal plasma (total and unbound) and CVS (total, dried spots) and HIV-RNA was quantified in paired blood and genital samples.

Results:

Among the 54 enrolled patients, 15 received maraviroc (6 men), 27 received raltegravir (14 men) and 20 received rilpivirine (10 men), corresponding to 54 total and 52 unbound plasma concentrations, 29 total CVS samples and 23 total and 18 unbound seminal plasma samples. Maraviroc and raltegravir displayed a ratio of genital fluids/plasma concentrations >0.5 in both male and female genital tracts. Conversely, rilpivirine displayed a low ratio. Antiretroviral free fractions were consistent with historical data. Nine patients had blood plasma HIV-RNA >50 copies/mL (2/9 had sub-optimal antiretroviral blood plasma exposure) and two other patients had detectable HIV-RNA in genital fluids.

Conclusions:

Maraviroc and raltegravir demonstrated good penetration in genital compartments, yielding good local virological response in genital compartments, whereas rilpivirine presented a low penetration profile but good local response.

PMID:
28961979
DOI:
10.1093/jac/dkx275
[Indexed for MEDLINE]

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