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: nnety-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: 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: 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.

Armenia, D., Spagnuolo, V., Bellocchi, M.c., Galli, L., Duca, L., Marchegiani, G., et al. (2024). 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 OF ANTIMICROBIAL CHEMOTHERAPY [10.1093/jac/dkae236].

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

Armenia, Daniele;Bellocchi, Maria C;Duca, Leonardo;Marchegiani, Greta;Carioti, Luca;Santoro, Maria
2024-07-15

Abstract

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: nnety-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: 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: 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.
15-lug-2024
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07
Settore MEDS-03/A - Microbiologia e microbiologia clinica
English
Armenia, D., Spagnuolo, V., Bellocchi, M.c., Galli, L., Duca, L., Marchegiani, G., et al. (2024). 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 OF ANTIMICROBIAL CHEMOTHERAPY [10.1093/jac/dkae236].
Armenia, D; Spagnuolo, V; Bellocchi, Mc; Galli, L; Duca, L; Marchegiani, G; Clemente, T; Carioti, L; Lolatto, R; Calza, L; Celesia, Bm; Cascio, A; Fra...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/375003
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