Four days/week antiretroviral maintenance strategy (ANRS 170 QUATUOR): substudies of reservoirs and ultrasensitive drug resistance.
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 06 2023
01 06 2023
Historique:
received:
28
12
2022
accepted:
04
04
2023
medline:
2
6
2023
pubmed:
27
4
2023
entrez:
27
4
2023
Statut:
ppublish
Résumé
In a 4 days/week (4/7 days) maintenance strategy (ANRS-170 QUATUOR trial), the virological impact of an intermittent strategy was assessed by ultrasensitive virological analyses of reservoirs and resistance. HIV-1 total DNA, ultra-sensitive plasma viral load (USpVL) and semen VL were measured in the first 121 participants. Sanger and ultra-deep sequencing (UDS) were performed on the HIV-1 genome (Illumina technology) according to the ANRS consensus. A generalized estimation equation with a Poisson distribution was used to compare changes in the proportion of residual viraemia, detectable semen HIV RNA and HIV DNA within and between the two groups over time. The proportion of participants with residual viraemia at Day 0 (D0) and Week 48 (W48) was 16.7% and 25.0% in the 4/7 days group and 22.4% and 29.7% in the 7/7 days group, respectively (+8.3% versus +7.3%, P = 0.971). The proportion of detectable DNA (>40 copies/106 cells) at D0 and W48 was 53.7% and 57.4% in the 4/7 days group and 56.1% and 51.8% in the 7/7 days group, respectively (+3.7% versus -4.3%, P = 0.358). Semen HIV RNA was detectable (≥100 copies/mL) in 2.2% of participants at D0 and 4.5% at W48 in the 4/7 days group versus 6.1% and 9.1% in the 7/7 days group, respectively (+2.3% versus +3.0%, P = 0.743). Emerging resistance at failure was more frequent in the 4/7 days group detected by Sanger sequencing: 3/6 participants versus 1/4 in the 7/7 days group, and similar with the UDS assay: 5/6 versus 4/4, respectively. These findings support the potency of a 4/7 days maintenance strategy on virological suppression at the reservoirs and emergent resistance level, including minority variants.
Sections du résumé
BACKGROUND
In a 4 days/week (4/7 days) maintenance strategy (ANRS-170 QUATUOR trial), the virological impact of an intermittent strategy was assessed by ultrasensitive virological analyses of reservoirs and resistance.
METHODS
HIV-1 total DNA, ultra-sensitive plasma viral load (USpVL) and semen VL were measured in the first 121 participants. Sanger and ultra-deep sequencing (UDS) were performed on the HIV-1 genome (Illumina technology) according to the ANRS consensus. A generalized estimation equation with a Poisson distribution was used to compare changes in the proportion of residual viraemia, detectable semen HIV RNA and HIV DNA within and between the two groups over time.
RESULTS
The proportion of participants with residual viraemia at Day 0 (D0) and Week 48 (W48) was 16.7% and 25.0% in the 4/7 days group and 22.4% and 29.7% in the 7/7 days group, respectively (+8.3% versus +7.3%, P = 0.971). The proportion of detectable DNA (>40 copies/106 cells) at D0 and W48 was 53.7% and 57.4% in the 4/7 days group and 56.1% and 51.8% in the 7/7 days group, respectively (+3.7% versus -4.3%, P = 0.358). Semen HIV RNA was detectable (≥100 copies/mL) in 2.2% of participants at D0 and 4.5% at W48 in the 4/7 days group versus 6.1% and 9.1% in the 7/7 days group, respectively (+2.3% versus +3.0%, P = 0.743). Emerging resistance at failure was more frequent in the 4/7 days group detected by Sanger sequencing: 3/6 participants versus 1/4 in the 7/7 days group, and similar with the UDS assay: 5/6 versus 4/4, respectively.
CONCLUSIONS
These findings support the potency of a 4/7 days maintenance strategy on virological suppression at the reservoirs and emergent resistance level, including minority variants.
Identifiants
pubmed: 37104815
pii: 7146011
doi: 10.1093/jac/dkad119
doi:
Substances chimiques
Anti-HIV Agents
0
Anti-Retroviral Agents
0
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1510-1521Investigateurs
Isabelle Lamaury
(I)
Emeline Duvallon
(E)
Firouzé Bani-Sadr
(F)
Isabelle Kmiec
(I)
Gilles Force
(G)
Amélie Chabrol
(A)
Nouara Agher
(N)
Fabienne Caby
(F)
Bouchra Wifaq
(B)
Olivier Patey
(O)
Anne Fresard
(A)
Amandine Gagneux-Brunon
(A)
Catherine Chirouze
(C)
Claudine Duvivier
(C)
Jérémie Lourenco
(J)
Violaine Tolsma
(V)
Cécile Janssen
(C)
Nathalie Lerolle
(N)
Pilartxo Catalan
(P)
Agathe Rami
(A)
Lucile De Ponthaud
(L)
Gilles Pichancourt
(G)
Safa Nasri
(S)
Stéphanie Landowski
(S)
Morgane Marcou
(M)
Julie Bottero
(J)
Flory Mfutila Kaykay
(F)
Gilles Pialoux
(G)
Olivier Bouchaud
(O)
Sophie Abgrall
(S)
Caroline Gatey
(C)
Laurence Weiss
(L)
Juliette Pavie
(J)
Dominique Salmonceron
(D)
David Zucman
(D)
Amina Fadli
(A)
Jean-Daniel Lelievre
(JD)
Romain Palich
(R)
Anne Simon
(A)
Dalila Beniken
(D)
Marie-Caroline Meyohas
(MC)
Julien Gras
(J)
André Cabie
(A)
Mathilde Pircher
(M)
Philippe Morlat
(P)
Mojgam Hessamfar
(M)
Didier Neau
(D)
Charles Cazenave
(C)
Claire Genet
(C)
Jean-François Faucher
(JF)
Djamila Makhloufi
(D)
André Boibieux
(A)
Sylvie Bregigeon-Ronot
(S)
Hélène Laroche
(H)
Aurélie Sautereau
(A)
Jacques Reynes
(J)
Alain Makinson
(A)
François Raffi
(F)
Olivier Bollengierstragier
(O)
Alissa Naqvi
(A)
Eric Cua
(E)
Eric Rosenthal
(E)
Sophie Breaud
(S)
Cédrick Arvieux
(C)
Jocelyne Vivent
(J)
Rodolphe Buzele
(R)
David Rey
(D)
Marie-Laure Batard
(ML)
Louis Bernard
(L)
Pierre Delobel
(P)
Marie Piffaut
(M)
Renaud Verdon
(R)
Lionel Piroth
(L)
Mathieu Blot
(M)
Pascale Leclercq
(P)
Anne Signori-Schmuck
(A)
Thomas Huleux
(T)
Agnès Meybeck
(A)
Thierry May
(T)
Mickael Delestan
(M)
Patrick Miailhes
(P)
Thomas Perpoint
(T)
Alix Greder-Belan
(A)
Dominique Bornarel
(D)
Brigitte Elharrar
(B)
Marie-Aude Khuong
(MA)
Marie Poupard
(M)
Laurent Blum
(L)
Christophe Michau
(C)
Carole Grand
(C)
Thierry Prazuck
(T)
Patrick Philibert
(P)
Barbara Gasse
(B)
Laurence Slama
(L)
Hitoto Hikombo
(H)
Iuliana Darasteanu
(I)
Françoise Itoua
(F)
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.