Decreased darunavir concentrations during once-daily co-administration with maraviroc and raltegravir: OPTIPRIM-ANRS 147 trial
Claire Pressiat
(1)
,
Déborah Hirt
(1)
,
Jean-Marc Treluyer
(1)
,
Yi Zheng
(1)
,
Philippe Morlat
(2, 3)
,
Philippe Morlat
(3)
,
Alice Naqvi
(4)
,
Laurent Tran
(5)
,
Jean-Paul Viard
(6, 7)
,
Véronique Avettand-Fenoel
(7, 8)
,
Christine Rouzioux
(7, 8)
,
Laurence Meyer
(5)
,
Antoine Cheret
(7, 9)
,
B Hoen
,
C Bourdeaux
,
J Delfraissy
,
C Goujard
,
I Amri
,
E Fourn
,
Y Quertainmont
,
M Môle
,
A Rami
,
A Durel
,
M Diemer
,
M Parrinello
,
T Allègre
,
A Lafeuillade
,
G Hittinger
,
V Lambry
,
M Carrerre
,
G Philip
,
C Duvivier
,
P Consigny
,
C Charlier
,
M Shoai
,
F Touam
,
G Pialoux
,
L Slama
,
T l'Yavanc
,
P Mathurin
,
A Adda
,
V Berrebi
,
D Salmon
,
E Chakvetadze
,
T Tassadit
,
E Ousseima
,
M Pietri
,
Y Levy
,
A Lascaux
,
J Lelievre
,
M Giovanna
,
S Dominguez
,
C Dumont
,
C Katlama
(10)
,
M Valentin
,
S Seang
,
L Schneider
(10)
,
N Kiorza
,
A Chermak
(10)
,
S Ben Abdallah
,
A Simon
,
F Pichon
,
M Pauchard
,
J Molina
,
C Lascoux
,
D Ponscarme
,
N Colin de Verdiere
,
A Scemla
,
N de Castro
,
A Rachline
,
V Garrait
,
W Rozenbaum
,
S Ferret
,
S Balkan
,
F Clavel
,
M Tourdjman
,
M Lafaurie
,
A Aslan
,
J Goguel
,
S Thierry
,
V de Lastours
,
S Gallien
,
J Pavie
,
J Delgado
,
C Mededji
,
R Veron
,
S Abel
,
S Pierre-François
,
C Baringhton
,
J Chennebault
,
Y Vandamme
,
P Fialaire
,
S Rehaiem
,
V Rabier
,
P Abgueguen
,
M Vandenhende
,
N Bernard
,
D Lacoste
,
C Michaux
,
F Paccalin
,
M Receveur
,
S Caldato
,
J Delaune
,
J Ragnaud
,
D Neau
,
L Lacaze-Buzy
,
J Livrozet
,
F Jeanblanc
,
D Makhloufi
,
F Brunel Dalmas
,
J Jourdain
,
P Chiarello
,
P Yeni
,
B Phung
,
C Rioux
,
C Godard
,
F Louni
,
N El Alami Talbi
,
G Catalano
,
F Guiroy
,
J Reynes
,
J Jacquet
,
V Fauchere
,
C Merle
,
V Lemoine
,
M Loriette
,
D Morquin
,
A Makinson
,
N Atoui
,
C Tramoni
,
F Raffi
,
C Allavena
,
B Bonnet
,
S Bouchez
,
N Feuillebois
,
C Brunet-François
,
V Reliquet
,
O Mounoury
,
P Morineau-Le-Houssine
,
E Billaud
,
D Brosseau
,
H Hüe
,
P Dellamonica
,
M Vassallo
,
A Leplatois
,
J Durant
,
A Joulié
,
F Souala
,
C Michelet
,
C Arvieux
,
P Tattevin
(11, 12)
,
H Leroy
,
M Revest
(12)
,
F Fily
,
J Chapplain
,
C Ratajczak
,
G Gras
,
L Bernard
,
J Dailloux
,
V Laplantine
,
L Cuzin
,
B Marchou
,
S Larrigue
,
M Chauveau
,
F Balsarin
,
M Obadia
,
S Bonne
,
T Huleux
,
F Ajana
,
I Alcaraz
,
V Baclet
,
H Melliez
,
N Viget
,
X de la Tribonniere
,
E Aissi
,
J Poissy
,
I Ravaux
,
A Vallon
,
M Varan
,
T May
,
L Letranchant
,
C Burty
,
A Briaud
,
S Wassoumbou
,
M Stenzel
,
M Bouillon
,
Y Debab
,
F Caron
,
I Gueit
,
C Chapuzet
,
F Borsa Lebas
,
M Etienne
,
P Miailhes
,
T Perpoint
,
A Senechal
,
I Schlienger
,
L Cotte
,
C Augustin Normand
,
A Boibieux
,
T Ferry
,
N Corsini
,
E Braun
,
J Lippran
,
F Biron
,
C Chidiac
,
S Pailhes
,
J Lipman
,
E Braun
,
J Koffi
,
V Thoirain
,
C Brochier
,
A Greder Belan
,
A Therby
,
S Monnier
,
M Ruquet
,
V Garrait
,
L Richier
,
F Prevoteau Du Clary
1
EA_7323 -
Evaluation thérapeutique et pharmacologie périnatale et pédiatrique
2 BPH - Bordeaux population health
3 Service de médecine interne et maladies infectieuses [Bordeaux]
4 Service de Maladies Infectieuses [CHU Nice]
5 CESP - Centre de recherche en épidémiologie et santé des populations
6 Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris]
7 EA 7327 - Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV)
8 Laboratoire de Virologie [CHU Necker]
9 Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre]
10 THERAVIR - Stratégies thérapeutiques contre l'infection VIH et les maladies virales associées [iPLesp]
11 BRM - ARN régulateurs bactériens et médecine
12 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
2 BPH - Bordeaux population health
3 Service de médecine interne et maladies infectieuses [Bordeaux]
4 Service de Maladies Infectieuses [CHU Nice]
5 CESP - Centre de recherche en épidémiologie et santé des populations
6 Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris]
7 EA 7327 - Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV)
8 Laboratoire de Virologie [CHU Necker]
9 Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre]
10 THERAVIR - Stratégies thérapeutiques contre l'infection VIH et les maladies virales associées [iPLesp]
11 BRM - ARN régulateurs bactériens et médecine
12 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Véronique Avettand-Fenoel
- Function : Author
- PersonId : 917126
- ORCID : 0000-0002-7022-2990
- IdRef : 09320955X
B Hoen
- Function : Author
C Bourdeaux
- Function : Author
J Delfraissy
- Function : Author
C Goujard
- Function : Author
I Amri
- Function : Author
E Fourn
- Function : Author
Y Quertainmont
- Function : Author
M Môle
- Function : Author
A Rami
- Function : Author
A Durel
- Function : Author
M Diemer
- Function : Author
M Parrinello
- Function : Author
T Allègre
- Function : Author
A Lafeuillade
- Function : Author
G Hittinger
- Function : Author
V Lambry
- Function : Author
M Carrerre
- Function : Author
G Philip
- Function : Author
C Duvivier
- Function : Author
P Consigny
- Function : Author
C Charlier
- Function : Author
M Shoai
- Function : Author
F Touam
- Function : Author
G Pialoux
- Function : Author
L Slama
- Function : Author
T l'Yavanc
- Function : Author
P Mathurin
- Function : Author
A Adda
- Function : Author
V Berrebi
- Function : Author
D Salmon
- Function : Author
E Chakvetadze
- Function : Author
T Tassadit
- Function : Author
E Ousseima
- Function : Author
M Pietri
- Function : Author
Y Levy
- Function : Author
A Lascaux
- Function : Author
J Lelievre
- Function : Author
M Giovanna
- Function : Author
S Dominguez
- Function : Author
C Dumont
- Function : Author
M Valentin
- Function : Author
S Seang
- Function : Author
- PersonId : 1213628
- IdHAL : sophie-seang
- ORCID : 0000-0001-7724-9312
N Kiorza
- Function : Author
S Ben Abdallah
- Function : Author
A Simon
- Function : Author
F Pichon
- Function : Author
M Pauchard
- Function : Author
J Molina
- Function : Author
C Lascoux
- Function : Author
D Ponscarme
- Function : Author
N Colin de Verdiere
- Function : Author
A Scemla
- Function : Author
N de Castro
- Function : Author
A Rachline
- Function : Author
V Garrait
- Function : Author
W Rozenbaum
- Function : Author
S Ferret
- Function : Author
S Balkan
- Function : Author
F Clavel
- Function : Author
M Tourdjman
- Function : Author
M Lafaurie
- Function : Author
A Aslan
- Function : Author
J Goguel
- Function : Author
S Thierry
- Function : Author
V de Lastours
- Function : Author
S Gallien
- Function : Author
J Pavie
- Function : Author
J Delgado
- Function : Author
C Mededji
- Function : Author
R Veron
- Function : Author
S Abel
- Function : Author
S Pierre-François
- Function : Author
C Baringhton
- Function : Author
J Chennebault
- Function : Author
Y Vandamme
- Function : Author
P Fialaire
- Function : Author
S Rehaiem
- Function : Author
V Rabier
- Function : Author
P Abgueguen
- Function : Author
M Vandenhende
- Function : Author
N Bernard
- Function : Author
D Lacoste
- Function : Author
C Michaux
- Function : Author
F Paccalin
- Function : Author
M Receveur
- Function : Author
S Caldato
- Function : Author
J Delaune
- Function : Author
J Ragnaud
- Function : Author
D Neau
- Function : Author
L Lacaze-Buzy
- Function : Author
J Livrozet
- Function : Author
F Jeanblanc
- Function : Author
D Makhloufi
- Function : Author
F Brunel Dalmas
- Function : Author
J Jourdain
- Function : Author
P Chiarello
- Function : Author
P Yeni
- Function : Author
B Phung
- Function : Author
C Rioux
- Function : Author
C Godard
- Function : Author
F Louni
- Function : Author
N El Alami Talbi
- Function : Author
G Catalano
- Function : Author
F Guiroy
- Function : Author
J Reynes
- Function : Author
J Jacquet
- Function : Author
V Fauchere
- Function : Author
C Merle
- Function : Author
V Lemoine
- Function : Author
M Loriette
- Function : Author
D Morquin
- Function : Author
A Makinson
- Function : Author
N Atoui
- Function : Author
C Tramoni
- Function : Author
F Raffi
- Function : Author
C Allavena
- Function : Author
B Bonnet
- Function : Author
S Bouchez
- Function : Author
N Feuillebois
- Function : Author
C Brunet-François
- Function : Author
V Reliquet
- Function : Author
O Mounoury
- Function : Author
P Morineau-Le-Houssine
- Function : Author
E Billaud
- Function : Author
D Brosseau
- Function : Author
H Hüe
- Function : Author
P Dellamonica
- Function : Author
M Vassallo
- Function : Author
A Leplatois
- Function : Author
J Durant
- Function : Author
A Joulié
- Function : Author
F Souala
- Function : Author
C Michelet
- Function : Author
C Arvieux
- Function : Author
H Leroy
- Function : Author
F Fily
- Function : Author
J Chapplain
- Function : Author
C Ratajczak
- Function : Author
G Gras
- Function : Author
L Bernard
- Function : Author
J Dailloux
- Function : Author
V Laplantine
- Function : Author
L Cuzin
- Function : Author
B Marchou
- Function : Author
- PersonId : 900564
- ORCID : 0000-0002-0673-2945
S Larrigue
- Function : Author
M Chauveau
- Function : Author
F Balsarin
- Function : Author
M Obadia
- Function : Author
S Bonne
- Function : Author
T Huleux
- Function : Author
F Ajana
- Function : Author
I Alcaraz
- Function : Author
V Baclet
- Function : Author
H Melliez
- Function : Author
N Viget
- Function : Author
X de la Tribonniere
- Function : Author
E Aissi
- Function : Author
J Poissy
- Function : Author
I Ravaux
- Function : Author
A Vallon
- Function : Author
M Varan
- Function : Author
T May
- Function : Author
L Letranchant
- Function : Author
C Burty
- Function : Author
A Briaud
- Function : Author
S Wassoumbou
- Function : Author
M Stenzel
- Function : Author
M Bouillon
- Function : Author
Y Debab
- Function : Author
F Caron
- Function : Author
I Gueit
- Function : Author
C Chapuzet
- Function : Author
F Borsa Lebas
- Function : Author
M Etienne
- Function : Author
P Miailhes
- Function : Author
T Perpoint
- Function : Author
A Senechal
- Function : Author
I Schlienger
- Function : Author
L Cotte
- Function : Author
C Augustin Normand
- Function : Author
A Boibieux
- Function : Author
T Ferry
- Function : Author
N Corsini
- Function : Author
E Braun
- Function : Author
J Lippran
- Function : Author
F Biron
- Function : Author
C Chidiac
- Function : Author
S Pailhes
- Function : Author
J Lipman
- Function : Author
E Braun
- Function : Author
J Koffi
- Function : Author
V Thoirain
- Function : Author
C Brochier
- Function : Author
A Greder Belan
- Function : Author
A Therby
- Function : Author
S Monnier
- Function : Author
M Ruquet
- Function : Author
V Garrait
- Function : Author
L Richier
- Function : Author
F Prevoteau Du Clary
- Function : Author
Abstract
Background
The OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values <50 copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we compared antiretroviral drug concentrations between the two arms.
Methods
Plasma samples were collected from 50 patients at various times after drug administration. A Bayesian approach based on published population pharmacokinetic models was used to estimate residual drug concentrations (Ctrough) and exposures (AUC) in each patient. A mixed linear regression model was then used to compare the AUC and Ctrough values of each drug used in both groups.
Results
Published models adequately described our data and could be used to predict Ctrough and AUC. No significant difference in tenofovir disoproxil fumarate, emtricitabine and ritonavir parameters was found between the two arms. However, darunavir Ctrough and AUC were significantly lower in the pentatherapy arm than in the tritherapy arm (P = 0.03 and P = 0.04, respectively).
Conclusions
Adding maraviroc and raltegravir to darunavir-based tritherapy decreased darunavir concentrations. Compliance issues, maraviroc–darunavir interaction and raltegravir–darunavir interaction were suspected and may affect the kinetics of viral decay during pentatherapy. A specific pharmacokinetic interaction study is needed to explore the interactions between darunavir and maraviroc and raltegravir.