Use of next-generation sequencing on HIV-1 DNA to assess archived resistance in highly treatment-experienced people with multidrug-resistant HIV under virological control: data from the PRESTIGIO Registry.
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:
15 Jul 2024
15 Jul 2024
Historique:
received:
12
02
2024
accepted:
22
06
2024
medline:
15
7
2024
pubmed:
15
7
2024
entrez:
15
7
2024
Statut:
aheadofprint
Résumé
To clarify whether next-generation sequencing (NGS) can be useful for resistance assessment in virologically suppressed highly treatment-experienced (HTE) individuals with MDR HIV. Ninety-one participants from the PRESTIGIO Registry were included. NGS was performed on HIV-DNA at 1%, 5% and 20% cut-offs; major drug resistance mutations (DRMs) were evaluated and compared with those detected in historical plasma genotypic resistance testing (h-GRT). APOBEC editing was also characterized. Participants had a complex and long treatment history [median 23 (IQR 21-25) years of ART exposure) and had been virologically suppressed since a median of 3 (IQR 2-5) years. Among all major DRMs detected by HIV-DNA NGS and/or h-GRT, 30% were exclusively found through NGS. The highest detection rate of historical major DRMs was reached with NGS set at 1%, but unusual substitutions and extensive APOBEC hypermutations suggest technical issues and poor clinical relevance in the 1%-5% interval. At NGS set at 5%, 67.2% of historical major DRMs were detected. The number of major DRMs detected exclusively by DNA-NGS as minority variants (frequency 5%-20%) was significantly higher in individuals who later experienced virological rebound compared with those who maintained virological control [median 2 (IQR 1-3) versus 1 (0-2), P = 0.030] and positively correlated with viraemia levels at rebound (rho = 0.474, P = 0.030). In non-viraemic people with an MDR virus, HIV-1 DNA NGS set at 5% is an acceptable technical cut-off that might help to reveal mutations with a potential clinical relevance. Moreover, the number of minority resistance mutations additionally detected by NGS might be associated with loss of virological control.
Sections du résumé
BACKGROUND
BACKGROUND
To clarify whether next-generation sequencing (NGS) can be useful for resistance assessment in virologically suppressed highly treatment-experienced (HTE) individuals with MDR HIV.
METHODS
METHODS
Ninety-one participants from the PRESTIGIO Registry were included. NGS was performed on HIV-DNA at 1%, 5% and 20% cut-offs; major drug resistance mutations (DRMs) were evaluated and compared with those detected in historical plasma genotypic resistance testing (h-GRT). APOBEC editing was also characterized.
RESULTS
RESULTS
Participants had a complex and long treatment history [median 23 (IQR 21-25) years of ART exposure) and had been virologically suppressed since a median of 3 (IQR 2-5) years. Among all major DRMs detected by HIV-DNA NGS and/or h-GRT, 30% were exclusively found through NGS. The highest detection rate of historical major DRMs was reached with NGS set at 1%, but unusual substitutions and extensive APOBEC hypermutations suggest technical issues and poor clinical relevance in the 1%-5% interval. At NGS set at 5%, 67.2% of historical major DRMs were detected. The number of major DRMs detected exclusively by DNA-NGS as minority variants (frequency 5%-20%) was significantly higher in individuals who later experienced virological rebound compared with those who maintained virological control [median 2 (IQR 1-3) versus 1 (0-2), P = 0.030] and positively correlated with viraemia levels at rebound (rho = 0.474, P = 0.030).
CONCLUSIONS
CONCLUSIONS
In non-viraemic people with an MDR virus, HIV-1 DNA NGS set at 5% is an acceptable technical cut-off that might help to reveal mutations with a potential clinical relevance. Moreover, the number of minority resistance mutations additionally detected by NGS might be associated with loss of virological control.
Identifiants
pubmed: 39004997
pii: 7713643
doi: 10.1093/jac/dkae236
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Gilead Sciences
Organisme : ViiV Healthcare
Organisme : Theratechnologies
Organisme : Merck Sharp & Dohme
Investigateurs
Antonella Castagna
(A)
Vincenzo Spagnuolo
(V)
Laura Galli
(L)
Franco Maggiolo
(F)
Leonardo Calza
(L)
Emanuele Focà
(E)
Filippo Lagi
(F)
Giovanni Cenderello
(G)
Antonio Di Biagio
(A)
Giulia Marchetti
(G)
Stefano Rusconi
(S)
Adriana Cervo
(A)
Roberta Gagliardini
(R)
Stefano Bonora
(S)
Anna Maria Cattelan
(AM)
Maurizio Zazzi
(M)
Maria Mercedes Santoro
(MM)
Maurizio Zazzi
(M)
Maria Mercedes Santoro
(MM)
Andrea Galli
(A)
Francesco Saladini
(F)
Daniele Armenia
(D)
Elisabetta Carini
(E)
Sabrina Bagaglio
(S)
Laura Galli
(L)
Riccardo Lolatto
(R)
Sara Diotallevi
(S)
Marcello Tavio
(M)
Alessandra Mataloni Paggi
(AM)
Francesca Vichi
(F)
Alessio Bellucci
(A)
Elisa Mirabelli
(E)
Annalisa Saracino
(A)
Flavia Balena
(F)
Franco Maggiolo
(F)
Laura Comi
(L)
Daniela Valenti
(D)
Claudia Suardi
(C)
Leonardo Calza
(L)
Federica Malerba
(F)
Francesco Castelli
(F)
Emanuele Focà
(E)
Davide Minisci
(D)
Francesca Pennati
(F)
Anna Celotti
(A)
Francesca Brognoli
(F)
Barbara Menzaghi
(B)
Maddalena Farinazzo
(M)
Bruno Cacopardo
(B)
Benedetto Maurizio Celesia
(BM)
Michele Salvatore Paternò Raddusa
(MSP)
Carmen Giarratana
(C)
Carlo Torti
(C)
Paolo Fusco
(P)
Gabriele Bruno
(G)
Angelo Pan
(A)
Paola Brambilla
(P)
Chiara Fornabaio
(C)
Alessandro Bartoloni
(A)
Susanna Giachè
(S)
Paola Corsi
(P)
Seble Tekle Kiros
(ST)
Filippo Lagi
(F)
Filippo Ducci
(F)
Teresa Santantonio
(T)
Sergio Lo Caputo
(SL)
Sergio Ferrara
(S)
Marianna Narducci
(M)
Emanuele Pontali
(E)
Marcello Feasi
(M)
Antonio Sarà
(A)
Matteo Bassetti
(M)
Antonio Di Biagio
(A)
Sabrina Blanchi
(S)
Antonella Castagna
(A)
Vincenzo Spagnuolo
(V)
Elisabetta Carini
(E)
Sabrina Bagaglio
(S)
Laura Galli
(L)
Riccardo Lolatto
(R)
Andrea Galli
(A)
Tommaso Clemente
(T)
Rebecka Papaioannu Borjesson
(RP)
Sara Diotallevi
(S)
Spinello Antinori
(S)
Tiziana Formenti
(T)
Andrea Giacomelli
(A)
Giulia Marchetti
(G)
Lidia Gazzola
(L)
Federica De Flaviis
(F)
Massimo Puoti
(M)
Cristina Moioli
(C)
Federico D'Amico
(F)
Cristina Mussini
(C)
Adriana Cervo
(A)
Roncaglia Enrica
(R)
Nardini Giulia
(N)
Barbara Beghetto
(B)
Elio Manzillo
(E)
Amedeo Lanzardo
(A)
Anna Maria Cattelan
(AM)
Maria Mazzitelli
(M)
Antonio Cascio
(A)
Marcello Trizzino
(M)
Elisa Fronti
(E)
Diletta Laccabue
(D)
Roberto Gulminetti
(R)
Andrea Zuccarini
(A)
Daniela Francisci
(D)
Elisabetta Schiaroli
(E)
Giuseppe De Socio
(G)
Elisa Garlassi
(E)
Romina Corsini
(R)
Roberta Gagliardini
(R)
Marisa Fusto
(M)
Loredana Sarmati
(L)
Vincenzo Malagnino
(V)
Silvia Lamonica
(S)
Simona Di Giambenedetto
(S)
Tiziana Mulas
(T)
Giovanni Cenderello
(G)
Rachele Pincino
(R)
Mario Tumbarello
(M)
Massimiliano Fabbiani
(M)
Francesca Panza
(F)
Ilaria Rancan
(I)
Giovanni Di Perri
(G)
Stefano Bonora
(S)
Micol Ferrara
(M)
Silvia Fantino
(S)
Marina Malena
(M)
Marta Fiscon
(M)
Informations de copyright
© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.