Long-term efficacy of dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: Week 96 results of ART-PRO pilot study.
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:
11 02 2021
11 02 2021
Historique:
received:
15
07
2020
accepted:
22
10
2020
pubmed:
18
11
2020
medline:
6
7
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
In the ART-PRO pilot trial there were no virological failures through 48 weeks of treatment with dolutegravir plus lamivudine in suppressed individuals with and without archived lamivudine resistance-associated mutations (RAMs) detected through next-generation sequencing (NGS) but without evidence of lamivudine RAMs in baseline proviral DNA population sequencing. To present 96 week results from ART-PRO. Open-label, single-arm pilot trial. At baseline, all participants switched to dolutegravir plus lamivudine. Participants were excluded if proviral DNA population genotyping detected lamivudine RAMs. To detect resistance minority variants, proviral DNA NGS was retrospectively performed from baseline samples. For this analysis the efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 96. Safety and tolerability outcomes were incidence of adverse events and treatment discontinuations. Forty-one participants were included, 21 with lamivudine RAMs in historical plasma RNA genotypes. Baseline proviral DNA NGS detected lamivudine RAMs (M184V/I and/or K65R/E/N) above a 5% threshold in 71.4% (15/21) and 15% (3/20) of participants with and without history of lamivudine resistance, respectively. At 96 weeks, 90.2% of participants achieved the efficacy endpoint. Between week 48 and 96 there was one discontinuation due to consent withdrawal and no discontinuations related to adverse events. Two participants had a transient viral rebound, both re-suppressed on dolutegravir plus lamivudine. Through week 96, there were no virological failures. In this pilot trial, dolutegravir plus lamivudine maintained virological suppression at 96 weeks despite historical lamivudine resistance and persisting archived minority lamivudine RAMs.
Sections du résumé
BACKGROUND
In the ART-PRO pilot trial there were no virological failures through 48 weeks of treatment with dolutegravir plus lamivudine in suppressed individuals with and without archived lamivudine resistance-associated mutations (RAMs) detected through next-generation sequencing (NGS) but without evidence of lamivudine RAMs in baseline proviral DNA population sequencing.
OBJECTIVES
To present 96 week results from ART-PRO.
METHODS
Open-label, single-arm pilot trial. At baseline, all participants switched to dolutegravir plus lamivudine. Participants were excluded if proviral DNA population genotyping detected lamivudine RAMs. To detect resistance minority variants, proviral DNA NGS was retrospectively performed from baseline samples. For this analysis the efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 96. Safety and tolerability outcomes were incidence of adverse events and treatment discontinuations.
RESULTS
Forty-one participants were included, 21 with lamivudine RAMs in historical plasma RNA genotypes. Baseline proviral DNA NGS detected lamivudine RAMs (M184V/I and/or K65R/E/N) above a 5% threshold in 71.4% (15/21) and 15% (3/20) of participants with and without history of lamivudine resistance, respectively. At 96 weeks, 90.2% of participants achieved the efficacy endpoint. Between week 48 and 96 there was one discontinuation due to consent withdrawal and no discontinuations related to adverse events. Two participants had a transient viral rebound, both re-suppressed on dolutegravir plus lamivudine. Through week 96, there were no virological failures.
CONCLUSIONS
In this pilot trial, dolutegravir plus lamivudine maintained virological suppression at 96 weeks despite historical lamivudine resistance and persisting archived minority lamivudine RAMs.
Identifiants
pubmed: 33200210
pii: 5983891
doi: 10.1093/jac/dkaa479
doi:
Substances chimiques
Anti-HIV Agents
0
Heterocyclic Compounds, 3-Ring
0
Oxazines
0
Piperazines
0
Pyridones
0
Lamivudine
2T8Q726O95
dolutegravir
DKO1W9H7M1
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
738-742Investigateurs
J R Arribas
(JR)
R De Miguel Buckley
(RM)
R Montejano
(R)
A Esteban-Cantos
(A)
N Stella-Ascariz
(N)
J Cadiñanos
(J)
M Mayoral
(M)
J M Castro
(JM)
V Moreno
(V)
L Martin-Carbonero
(L)
E Valencia
(E)
I Bernardino
(I)
C Busca
(C)
R Micán
(R)
I Pérez-Valero
(I)
J González
(J)
M L Montes
(ML)
J Rodríguez Centeno
(JR)
F Pulido
(F)
D Rial-Crestelo
(D)
L Dominguez-Dominguez
(L)
P Aranguren-Rivas
(P)
O Bisbal
(O)
L Bermejo Plaza
(LB)
M Garcia-Alvarez
(M)
M Santacreu-Guerrero
(M)
M de Lagarde
(M)
M Matarranz
(M)
J Luzckoviak
(J)
A Sotillo
(A)
R Delgado
(R)
R Rubio
(R)
Informations de copyright
© The Author(s) 2020. 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.