Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018.
Details
State: Public
Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_B803006D685B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018.
Journal
The Journal of antimicrobial chemotherapy
Working group(s)
Swiss HIV Cohort Study
Contributor(s)
Anagnostopoulos A., Battegay M., Bernasconi E., Böni J., Braun D.L., Bucher H.C., Calmy A., Cavassini M., Ciuffi A., Dollenmaier G., Egger M., Elzi L., Fehr J., Fellay J., Furrer H., Fux C.A., Günthard H., Haerry D., Hasse B., Hirsch H.H., Hoffmann M., Hösli I., Huber M., Kahlert C.R., Kaiser L., Keiser O., Klimkait T., Kouyos R.D., Kovari H., Kusejko K., Ledergerber B., Martinetti G., Martinez de Tejada B., Marzolini C., Metzner K.J., Müller N., Nicca D., Paioni P., Pantaleo G., Perreau M., Rauch A., Rudin C., Schmid P., Speck R., Stöckle M., Tarr P., Trkola A., Vernazza P., Wandeler G., Weber R., Yerly S.
ISSN
1460-2091 (Electronic)
ISSN-L
0305-7453
Publication state
Published
Issued date
05/09/2023
Peer-reviewed
Oui
Volume
78
Number
9
Pages
2323-2334
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Genotypic resistance testing (GRT) is routinely performed upon diagnosis of HIV-1 infection or during virological failure using plasma viral RNA. An alternative source for GRT could be cellular HIV-1 DNA.
A substantial number of participants in the Swiss HIV Cohort Study (SHCS) never received GRT. We applied a method that enables access to the near full-length proviral HIV-1 genome without requiring detectable viraemia.
Nine hundred and sixty-two PBMC specimens were received. Our two-step nested PCR protocol was applied to generate two overlapping long-range amplicons of the HIV-1 genome, sequenced by next-generation sequencing (NGS) and analysed by MinVar, a pipeline to detect drug resistance mutations (DRMs).
Six hundred and eighty-one (70.8%) of the samples were successfully amplified, sequenced and analysed by MinVar. Only partial information of the pol gene was contained in 82/681 (12%), probably due to naturally occurring deletions in the proviral sequence. All common HIV-1 subtypes were successfully sequenced. We detected at least one major DRM at high frequency (≥15%) in 331/599 (55.3%) individuals. Excluding APOBEC-signature (G-to-A mutation) DRMs, 145/599 (24.2%) individuals carried at least one major DRM. RT-inhibitor DRMs were most prevalent. The experienced time on ART was significantly longer in DRM carriers (P = 0.001) independent of inclusion or exclusion of APOBEC-signature DRMs.
We successfully applied a reliable and efficient method to analyse near full-length HIV-1 proviral DNA and investigated DRMs in individuals with undetectable or low viraemia. Additionally, our data underscore the need for new computational tools to exclude APOBEC-related hypermutated NGS sequence reads for reporting DRMs.
A substantial number of participants in the Swiss HIV Cohort Study (SHCS) never received GRT. We applied a method that enables access to the near full-length proviral HIV-1 genome without requiring detectable viraemia.
Nine hundred and sixty-two PBMC specimens were received. Our two-step nested PCR protocol was applied to generate two overlapping long-range amplicons of the HIV-1 genome, sequenced by next-generation sequencing (NGS) and analysed by MinVar, a pipeline to detect drug resistance mutations (DRMs).
Six hundred and eighty-one (70.8%) of the samples were successfully amplified, sequenced and analysed by MinVar. Only partial information of the pol gene was contained in 82/681 (12%), probably due to naturally occurring deletions in the proviral sequence. All common HIV-1 subtypes were successfully sequenced. We detected at least one major DRM at high frequency (≥15%) in 331/599 (55.3%) individuals. Excluding APOBEC-signature (G-to-A mutation) DRMs, 145/599 (24.2%) individuals carried at least one major DRM. RT-inhibitor DRMs were most prevalent. The experienced time on ART was significantly longer in DRM carriers (P = 0.001) independent of inclusion or exclusion of APOBEC-signature DRMs.
We successfully applied a reliable and efficient method to analyse near full-length HIV-1 proviral DNA and investigated DRMs in individuals with undetectable or low viraemia. Additionally, our data underscore the need for new computational tools to exclude APOBEC-related hypermutated NGS sequence reads for reporting DRMs.
Keywords
Drug Resistance, Viral, HIV-1/drug effects, DNA/genetics, Mutation, Switzerland/epidemiology, HIV Infections/drug therapy, HIV Infections/epidemiology, Retrospective Studies, Humans, Male, Female, Adult, Middle Aged, DNA-Directed DNA Polymerase/metabolism, Prevalence
Pubmed
Web of science
Open Access
Yes
Create date
10/08/2023 14:31
Last modification date
09/08/2024 16:05