Investigation of drug resistance against protease, reverse transcriptase, and integrase inhibitors by next‐generation sequencing in HIV‐positive patients

Tekin, Duygu; Gökengin, Deniz; Onay, H; Erensoy, Selda; Sertöz, Rüçhan

doi:10.1002/jmv.26582

Cited by 7 publications

(4 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clinical relationship between HIV minority resistance variants and disease is still inconclusive, but it has been documented that minority resistance variants may lead to the failure of HIV virological treatment ( Gupta et al, 2014 ; Hikichi et al, 2021 ). Population-based studies have proven that NGS can detect a large proportion of low-level variants, while traditional Sanger sequencing cannot detect ( Baxter et al, 2021 ; Tekin et al, 2021 ). Similarly, the same conclusion was obtained in our study.…”

Section: Discussionmentioning

confidence: 99%

Establishment and application of a method of tagged-amplicon deep sequencing for low-abundance drug resistance in HIV-1

Han

Wang

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

In the latest HIV-1 global drug resistance report released by WHO, countries are advised to strengthen pre-treatment monitoring of drug resistance in AIDS patients. In this study, we established an NGS-based segmented amplification HIV-1 drug resistance mutation detection method. The pol region of HIV-1 was divided into three short fragments for NGS. The entire amplification and sequencing panel were more cost-effective and batched by using the barcode sequence corresponding to the sample. Each parameter was evaluated using samples with known resistance variants frequencies. The nucleotide sequence error rate, amino acid error rate, and noise value of the NGS-based segmented amplification method were both less than 1%. When the threshold was 2%, the consensus sequences of the HIV-1 NL4-3 strain were completely consistent with the Sanger sequences. This method can detect the minimum viral load of the sample at 102 copies/ml, and the input frequency and detection frequency of HIV-1 resistance mutations within the range of 1%–100% had good conformity (R2 = 0.9963; R2 = 0.9955). This method had no non-specific amplification for Hepatitis B and C. Under the 2% threshold, the incidence of surveillance drug resistance mutations in ART-naive HIV-infected patients was 20.69%, among which NRTIs class resistance mutations were mainly.

show abstract

Section: Discussionmentioning

confidence: 99%

Establishment and application of a method of tagged-amplicon deep sequencing for low-abundance drug resistance in HIV-1

Han

Wang

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…If the main treatment component of choice is not suitable for PLWHA, it can be changed to alternative treatment. For example, in pregnant female patients with low CD4+ (≤ 50 cells/µL), PLWHA with comorbid neurocognitive disorders, chronic kidney disease, cardiovascular disease, or chronic hepatitis, alternative ART regimens can be considered (Tekin, et al, 2021).…”

Section: Hiv Drug Resistance (Art)mentioning

confidence: 99%

Resistance To Antiretroviral Therapy In People With HIV

Asryadin,

Yuniati,

Panjenengan

et al. 2023

jppipa, pendidikan ipa, fisika, biologi, kimia

View full text Add to dashboard Cite

Human Immunodeficiency Virus (HIV) is a virus that damages the immune system, and has RNA genetic material which is converted by the reverse transcriptase enzyme into DNA. This research aims to determine the existence of resistance by identifying mutations related to drug resistance in HIV-1, especially in the genes encoding the PR and RT enzymes which are the targets of ARVs. This research uses the observational method. Research data analysis was carried out in the form of descriptive data analysis of the output of each formula based on the results of HIV measurements. This study contains a series of reviews that focus on the topic and incidence and possibility of HIV drug resistance (ART) in PLHIV/PLWHA. The main and important thing in detecting the possibility of resistance to ARV therapy is by examining the genotype and phenotype. Standardization between laboratories for drug resistance studies through the use of various methods, especially to identify mixed bases that cause estimated resistance mutations. Additionally, sequencing of protease, RT, and/or integrase is used to identify the clinical significance of DRM. There are two genetic mechanisms of NRTI resistance, namely: (1) discriminative mutations that activate RT to differentiate between the dideoxy-NRTI chain terminator and the cell's own dNTP; and (2) unblocking mutations that facilitate phosphorylytic excision of NRTI-triphosphate from viral DNA. Blocking mutations are also referred to as thymidine analogue mutations (TAMs). ARV resistance can be detected by examining the virus genotype which aims to determine the occurrence of mutations in one of the virus codons compared to ARV-sensitive wild type HIV-1 and by in vitro phenotyping, where this method takes quite a long time and is usually focused on finding a regimen new drug

show abstract

“…Sanger sequencing is a population-based method that uses a di-deoxy chain termination chemistry to generate a single consensus sequence representative of the most common bases at each nucleotide position [7]. This, however, means that Sanger sequencing does not reliably detect mutations that are less represented within the viral pool, also known as low-abundance drug-resistant variants (LA-DRVs) [8,9]. Despite that, HIVDR mutations detected by Sanger sequencing have been shown to predict treatment response, making it a reliable method for use in making clinical decisions [10].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Drug Resistance Genotyping in Resource Limited Settings: Current and Future Perspectives in Sequencing Technologies

Manyana

Gounder

Pillay

et al. 2021

Viruses

View full text Add to dashboard Cite

Affordable, sensitive, and scalable technologies are needed for monitoring antiretroviral treatment (ART) success with the goal of eradicating HIV-1 infection. This review discusses use of Sanger sequencing and next generation sequencing (NGS) methods for HIV-1 drug resistance (HIVDR) genotyping, focusing on their use in resource limited settings (RLS). Sanger sequencing remains the gold-standard method for detecting HIVDR mutations of clinical relevance but is mainly limited by high sequencing costs and low-throughput. NGS is becoming a more common sequencing method, with the ability to detect low-abundance drug-resistant variants and reduce per sample costs through sample pooling and massive parallel sequencing. However, use of NGS in RLS is mainly limited by infrastructure costs. Given these shortcomings, our review discusses sequencing technologies for HIVDR genotyping, focusing on common in-house and commercial assays, challenges with Sanger sequencing in keeping up with changes in HIV-1 treatment programs, as well as challenges with NGS that limit its implementation in RLS and in clinical diagnostics. We further discuss knowledge gaps and offer recommendations on how to overcome existing barriers for implementing HIVDR genotyping in RLS, to make informed clinical decisions that improve quality of life for people living with HIV.

show abstract

Investigation of drug resistance against protease, reverse transcriptase, and integrase inhibitors by next‐generation sequencing in HIV‐positive patients

Cited by 7 publications

References 31 publications

Establishment and application of a method of tagged-amplicon deep sequencing for low-abundance drug resistance in HIV-1

Establishment and application of a method of tagged-amplicon deep sequencing for low-abundance drug resistance in HIV-1

Resistance To Antiretroviral Therapy In People With HIV

HIV-1 Drug Resistance Genotyping in Resource Limited Settings: Current and Future Perspectives in Sequencing Technologies

Contact Info

Product

Resources

About