Towards Next-Generation Sequencing for HIV-1 Drug Resistance Testing in a Clinical Setting
The HIV genotypic resistance test (GRT) is a standard of care for the clinical management of HIV/AIDS patients. In recent decades, population or Sanger sequencing has been the foundation for drug resistance monitoring in clinical settings. However, the advent of high-throughput or next-generation se...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/14/10/2208 |
| _version_ | 1827647715836690432 |
|---|---|
| author | Calesta Hui Yi Teo Nurul Hannah Binte Norhisham Ogestelli Fabia Lee Siyu Png Chean Nee Chai Gabriel Yan Julian Wei-Tze Tang Chun Kiat Lee |
| author_facet | Calesta Hui Yi Teo Nurul Hannah Binte Norhisham Ogestelli Fabia Lee Siyu Png Chean Nee Chai Gabriel Yan Julian Wei-Tze Tang Chun Kiat Lee |
| author_sort | Calesta Hui Yi Teo |
| collection | DOAJ |
| description | The HIV genotypic resistance test (GRT) is a standard of care for the clinical management of HIV/AIDS patients. In recent decades, population or Sanger sequencing has been the foundation for drug resistance monitoring in clinical settings. However, the advent of high-throughput or next-generation sequencing has caused a paradigm shift towards the detection and characterization of low-abundance covert mutations that would otherwise be missed by population sequencing. This is clinically significant, as these mutations can potentially compromise the efficacy of antiretroviral therapy, causing poor virologic suppression. Therefore, it is important to develop a more sensitive method so as to reliably detect clinically actionable drug-resistant mutations (DRMs). Here, we evaluated the diagnostic performance of a laboratory-developed, high-throughput, sequencing-based GRT using 103 archived clinical samples that were previously tested for drug resistance using population sequencing. As expected, high-throughput sequencing found all the DRMs that were detectable by population sequencing. Significantly, 78 additional DRMs were identified only by high-throughput sequencing, which is statistically significant based on McNemar’s test. Overall, our results complement previous studies, supporting the notion that the two methods are well correlated, and the high-throughput sequencing method appears to be an excellent alternative for drug resistance testing in a clinical setting. |
| first_indexed | 2024-03-09T19:22:50Z |
| format | Article |
| id | doaj.art-51c583d28acd42f38f3ad0b4a780dfd4 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T19:22:50Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-51c583d28acd42f38f3ad0b4a780dfd42023-11-24T03:09:23ZengMDPI AGViruses1999-49152022-10-011410220810.3390/v14102208Towards Next-Generation Sequencing for HIV-1 Drug Resistance Testing in a Clinical SettingCalesta Hui Yi Teo0Nurul Hannah Binte Norhisham1Ogestelli Fabia Lee2Siyu Png3Chean Nee Chai4Gabriel Yan5Julian Wei-Tze Tang6Chun Kiat Lee7Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, SingaporeSchool of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Singapore 599490, SingaporeSchool of Life and Physical Sciences, PSB Academy, Singapore 039594, SingaporeDepartment of Laboratory Medicine, National University Health System, Singapore 119228, SingaporeDepartment of Laboratory Medicine, National University Health System, Singapore 119228, SingaporeDepartment of Medicine, National University Health System, Singapore 119228, SingaporeRespiratory Sciences, University of Leicester, Leicester LE1 7RH, UKDepartment of Laboratory Medicine, National University Health System, Singapore 119228, SingaporeThe HIV genotypic resistance test (GRT) is a standard of care for the clinical management of HIV/AIDS patients. In recent decades, population or Sanger sequencing has been the foundation for drug resistance monitoring in clinical settings. However, the advent of high-throughput or next-generation sequencing has caused a paradigm shift towards the detection and characterization of low-abundance covert mutations that would otherwise be missed by population sequencing. This is clinically significant, as these mutations can potentially compromise the efficacy of antiretroviral therapy, causing poor virologic suppression. Therefore, it is important to develop a more sensitive method so as to reliably detect clinically actionable drug-resistant mutations (DRMs). Here, we evaluated the diagnostic performance of a laboratory-developed, high-throughput, sequencing-based GRT using 103 archived clinical samples that were previously tested for drug resistance using population sequencing. As expected, high-throughput sequencing found all the DRMs that were detectable by population sequencing. Significantly, 78 additional DRMs were identified only by high-throughput sequencing, which is statistically significant based on McNemar’s test. Overall, our results complement previous studies, supporting the notion that the two methods are well correlated, and the high-throughput sequencing method appears to be an excellent alternative for drug resistance testing in a clinical setting.https://www.mdpi.com/1999-4915/14/10/2208HIV-1drug resistancegenotypic resistance testingnext-generation sequencinghigh-throughput sequencingSanger |
| spellingShingle | Calesta Hui Yi Teo Nurul Hannah Binte Norhisham Ogestelli Fabia Lee Siyu Png Chean Nee Chai Gabriel Yan Julian Wei-Tze Tang Chun Kiat Lee Towards Next-Generation Sequencing for HIV-1 Drug Resistance Testing in a Clinical Setting Viruses HIV-1 drug resistance genotypic resistance testing next-generation sequencing high-throughput sequencing Sanger |
| title | Towards Next-Generation Sequencing for HIV-1 Drug Resistance Testing in a Clinical Setting |
| title_full | Towards Next-Generation Sequencing for HIV-1 Drug Resistance Testing in a Clinical Setting |
| title_fullStr | Towards Next-Generation Sequencing for HIV-1 Drug Resistance Testing in a Clinical Setting |
| title_full_unstemmed | Towards Next-Generation Sequencing for HIV-1 Drug Resistance Testing in a Clinical Setting |
| title_short | Towards Next-Generation Sequencing for HIV-1 Drug Resistance Testing in a Clinical Setting |
| title_sort | towards next generation sequencing for hiv 1 drug resistance testing in a clinical setting |
| topic | HIV-1 drug resistance genotypic resistance testing next-generation sequencing high-throughput sequencing Sanger |
| url | https://www.mdpi.com/1999-4915/14/10/2208 |
| work_keys_str_mv | AT calestahuiyiteo towardsnextgenerationsequencingforhiv1drugresistancetestinginaclinicalsetting AT nurulhannahbintenorhisham towardsnextgenerationsequencingforhiv1drugresistancetestinginaclinicalsetting AT ogestellifabialee towardsnextgenerationsequencingforhiv1drugresistancetestinginaclinicalsetting AT siyupng towardsnextgenerationsequencingforhiv1drugresistancetestinginaclinicalsetting AT cheanneechai towardsnextgenerationsequencingforhiv1drugresistancetestinginaclinicalsetting AT gabrielyan towardsnextgenerationsequencingforhiv1drugresistancetestinginaclinicalsetting AT julianweitzetang towardsnextgenerationsequencingforhiv1drugresistancetestinginaclinicalsetting AT chunkiatlee towardsnextgenerationsequencingforhiv1drugresistancetestinginaclinicalsetting |