Integrase strand transfer inhibitors and neuropsychiatric adverse events in a large prospective cohort.
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
Cohort Studies
Female
France
/ epidemiology
HIV Infections
/ complications
HIV Integrase Inhibitors
/ adverse effects
Heterocyclic Compounds, 3-Ring
/ adverse effects
Humans
Male
Mental Disorders
/ epidemiology
Nervous System Diseases
/ epidemiology
Oxazines
Piperazines
Prospective Studies
Public Health Surveillance
Pyridones
Quinolones
/ adverse effects
Raltegravir Potassium
/ adverse effects
Viral Load
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:
01 03 2019
01 03 2019
Historique:
received:
11
05
2018
revised:
02
11
2018
accepted:
08
11
2018
pubmed:
12
12
2018
medline:
4
6
2020
entrez:
12
12
2018
Statut:
ppublish
Résumé
To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs). Patients in 18 HIV reference centres in France were prospectively included in the Dat'AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients' characteristics related to discontinuation due to NPAEs were sought. INSTIs were prescribed to 21315 patients: 6274 received dolutegravir, 3421 received elvitegravir boosted by cobicistat, and 11620 received raltegravir. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the dolutegravir-, elvitegravir- and raltegravir-treated patients, respectively (P < 0.001). Discontinuation for NPAEs occurred in 2.7%, 1.3% and 1.7% of the dolutegravir-, elvitegravir-, and raltegravir-treated patients, respectively (P < 0.001). In the multivariate analysis, discontinuation for NPAEs was related to dolutegravir versus elvitegravir (HR = 2.27; 95% CI 1.63-3.17; P < 0.0001) and versus raltegravir (HR = 2.46; 95% CI 2.00-3.40; P < 0.0001), but neither gender (HR for women = 1.19; 95% CI 0.97-1.46; P = 0.09) nor age (P = 0.12) was related. The association with abacavir was not retained in the final model. Although discontinuation for side effects was less frequent with dolutegravir than with boosted elvitegravir, discontinuation for NPAEs, although rare (2.7%), was more frequent with dolutegravir. No patient characteristic was found to be associated with these side effects in this very large population.
Identifiants
pubmed: 30534993
pii: 5232558
doi: 10.1093/jac/dky497
doi:
Substances chimiques
HIV Integrase Inhibitors
0
Heterocyclic Compounds, 3-Ring
0
Oxazines
0
Piperazines
0
Pyridones
0
Quinolones
0
Raltegravir Potassium
43Y000U234
elvitegravir
4GDQ854U53
dolutegravir
DKO1W9H7M1
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
754-760Investigateurs
C Drobacheff-Thiébaut
(C)
A Foltzer
(A)
K Bouiller
(K)
L Hustache-Mathieu
(L)
C Chirouze
(C)
Q Lepiller
(Q)
F Bozon
(F)
O Babre
(O)
P Muret
(P)
H Laurichesse
(H)
O Lesens
(O)
M Vidal
(M)
N Mrozek
(N)
C Aumeran
(C)
O Baud
(O)
V Corbin
(V)
P Letertre
(P)
S Casanova
(S)
C Jacomet
(C)
B Hoen
(B)
I Lamaury
(I)
I Fabre
(I)
E Curlier
(E)
R Ouissa
(R)
K Schepers
(K)
C Herrmann-Storck
(C)
N Dournon
(N)
D Merrien
(D)
P Perré
(P)
T Guimard
(T)
O Bollangier
(O)
S Leautez
(S)
M Morrier
(M)
F Ader
(F)
F Biron
(F)
A Boibieux
(A)
L Cotte
(L)
T Ferry
(T)
P Miailhes
(P)
T Perpoint
(T)
S Roux
(S)
S Degroodt
(S)
C Brochier
(C)
F Valour
(F)
C Chidiac
(C)
C Dhiver
(C)
M Saadia Mokhtari
(M)
A Ménard
(A)
H Tissot Dupont
(H)
C Toméi
(C)
L Meddeb
(L)
A Y Belkhir
(AY)
I Ravaux
(I)
S Brégigeon
(S)
O Zaegel-Faucher
(O)
V Obry-Roguet
(V)
M Orticoni
(M)
M J Soavi
(MJ)
I Luquet-Besson
(I)
E Ressiot
(E)
M Carta-Padovani
(M)
M J Ducassou
(MJ)
H Bertone
(H)
S Galie
(S)
A Galinier
(A)
M Monclar
(M)
A S Ritleng
(AS)
A Ivanova
(A)
C Blanco-Betancourt
(C)
C Lions
(C)
I Poizot-Martin
(I)
S Abel
(S)
R Césaire
(R)
L Cuzin
(L)
G Dos Santos
(G)
L Fagour
(L)
M Illiaquer
(M)
F Najioullah
(F)
D Nguyen
(D)
M Ouka
(M)
S Pierre-François
(S)
J Pasquier
(J)
M Pircher
(M)
B Rozé
(B)
A Cabié
(A)
N Atoui
(N)
V Le Moing
(V)
A Makinson
(A)
N Meftah
(N)
C Merle de Boever
(C)
B Montes
(B)
A Montoya Ferrer
(A)
J Reynes
(J)
M André
(M)
L Boyer
(L)
M P Bouillon
(MP)
M Delestan
(M)
T May
(T)
C Allavena
(C)
C Bernaud
(C)
E Billaud
(E)
C Biron
(C)
B Bonnet
(B)
S Bouchez
(S)
D Boutoille
(D)
C Brunet-Cartier
(C)
N Hall
(N)
T Jovelin
(T)
P Morineau
(P)
V Reliquet
(V)
H Hue
(H)
S Sécher
(S)
M Cavellec
(M)
A Soria
(A)
V Ferré
(V)
E André-Garnier
(E)
A Rodallec
(A)
L Le Guen
(L)
M Lefebvre
(M)
O Grossi
(O)
P Point
(P)
O Aubry
(O)
L Khatchatourian
(L)
F Raffi
(F)
P Pugliese
(P)
S Breaud
(S)
C Ceppi
(C)
J Courjon
(J)
E Cua
(E)
J Cottalorda
(J)
P Dellamonica
(P)
E Demonchy
(E)
A De Monte
(A)
J Durant
(J)
C Etienne
(C)
S Ferrando
(S)
J G Fuzibet
(JG)
R Garraffo
(R)
A Joulie
(A)
K Risso
(K)
V Mondain
(V)
A Naqvi
(A)
N Oran
(N)
I Perbost
(I)
S Pillet
(S)
B Prouvost-Keller
(B)
C Pradier
(C)
S Wehrlen-Pugliese
(S)
V Rio
(V)
E Rosenthal
(E)
S Sausse
(S)
G Zouzou
(G)
L Hocqueloux
(L)
A Cheret
(A)
C Goujard
(C)
Y Quertainmont
(Y)
E Teicher
(E)
N Lerolle
(N)
D Vittecoq
(D)
O Deradji
(O)
F Fourreau
(F)
C Pallier
(C)
A Barrail-Tran
(A)
R Landman
(R)
V Joly
(V)
C Rioux
(C)
S Lariven
(S)
A Gervais
(A)
F X Lescure
(FX)
S Matheron
(S)
F Louni
(F)
C Godard
(C)
Z Julia
(Z)
M Chansombat
(M)
D Rahli
(D)
C Mackoumbou-Nkouka
(C)
C Charpentier
(C)
D Descamps
(D)
G Peytavin
(G)
Y Yazdanpanah
(Y)
P H Consigny
(PH)
G Cessot
(G)
P Bossi
(P)
J Goesch
(J)
J Gilquin
(J)
G Benabdelmoumen
(G)
F Lanternier
(F)
C Charlier
(C)
K Amazzough
(K)
B Henry
(B)
B Pilmis
(B)
C Rouzaud
(C)
M Morgand
(M)
F Touam
(F)
C Louisin
(C)
C Duvivier
(C)
O Lortholary
(O)
R Guery
(R)
F Danion
(F)
J Lourenco
(J)
P Parize
(P)
N Etienne
(N)
M Launay
(M)
C Rouzioux
(C)
V Avettand Fenoel
(V)
M A Valantin
(MA)
P Flandre
(P)
F Caby
(F)
R Tubiana
(R)
R Agher
(R)
S Seang
(S)
L Schneider
(L)
R Palich
(R)
C Blanc
(C)
C Katlama
(C)
J L Berger
(JL)
Y N’Guyen
(Y)
D Lambert
(D)
D Lebrun
(D)
I Kmiec
(I)
M Hentzien
(M)
V Brodard
(V)
F Bani-Sadr
(F)
E Botelho-Nevers
(E)
A Gagneux-Brunon
(A)
A Frésard
(A)
F Lucht
(F)
P Fischer
(P)
M Partisani
(M)
C Cheneau
(C)
M Priester
(M)
M L Batard
(ML)
C Bernard-Henry
(C)
E de Mautort
(E)
D Rey
(D)
M Alvarez
(M)
N Biezunski
(N)
A Debard
(A)
C Delpierre
(C)
P Lansalot
(P)
L Lelièvre
(L)
G Martin-Blondel
(G)
D Metsu
(D)
M Piffaut
(M)
L Porte
(L)
K Saune
(K)
P Delobel
(P)
F Ajana
(F)
I Alcaraz
(I)
V Baclet
(V)
A Boucher
(A)
P Choisy
(P)
T Huleux
(T)
B Lafon-Desmurs
(B)
H Melliez
(H)
A Meybeck
(A)
A Pasquet
(A)
M Pradier
(M)
O Robineau
(O)
N Viget
(N)
M Valette
(M)
Informations de copyright
© The Author(s) 2018. 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.