| Autor: |
Jaha, Bashkim, Schenkel, Corinne D, Jörimann, Lisa, Huber, Michael, Zaheri, Maryam, Neumann, Kathrin, Leemann, Christine, Calmy, Alexandra, Cavassini, Matthias, Kouyos, Roger D, Günthard, Huldrych F, Metzner, Karin J, Study, Swiss HIV Cohort |
| Předmět: |
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| Zdroj: |
Journal of Antimicrobial Chemotherapy (JAC); Sep2023, Vol. 78 Issue 9, p2323-2334, 12p |
| Abstrakt: |
Background 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. Objectives 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. Methods 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). Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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