Quality Control of Next-Generation Sequencing-Based HIV-1 Drug Resistance Data in Clinical Laboratory Information Systems Framework

Capiña, Rupert; Li, Katherine; Kearney, Levon; Vandamme, Anne‐Mieke; Harrigan, P. Richard; Laethem, Kristel Van

doi:10.3390/v12060645

Cited by 9 publications

(5 citation statements)

References 46 publications

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“…15,16 Standard method for HIVDR genotyping, Sanger sequencing, produced a consistent sequence, using a detection threshold of approximately 15%-20%; however, this prevents minority resistance from detecting variants below this frequency threshold. 17 To determine whether the presence of minority variants resulted in a high rate of VF in the PPDG, the baseline plasma of 26 patients with VF in the PPDG were detected by NGS. We find some mutations that were not detected by Sanger sequencing, but only 3 cases with these mutations showed single low-level or intermediate-level resistance to EFV, 1 to TDF, and 1 to 3TC and TDF.…”

Section: Discussion the Pretreatment Potential Resistance Of Nnrtis A...mentioning

confidence: 99%

The Effect of Pretreatment Potential Resistance to NNRTIs on Antiviral Therapy in Patients With HIV/AIDS

Xiao

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: With the increasing coverage of antiretroviral therapy, concerns for the emergence and transmission of HIV drug resistance (HIVDR) are arising. HIVDR was divided into 5 levels: sensitive, potentially resistant, low resistant, intermediate resistant, and high resistant. Most of the articles on HIVDR involved lowlevel, intermediate-level, and high-level drug resistance to antiretroviral drug, and few articles deal with potential drug resistance. Treatment failure associated with the level of low-level, intermediate-level, and high-level resistance to antiretroviral drug has been reported. However, whether virological failure (VF) is related to potential resistance remains unclear. In this study, we aimed to describe the situation of potential resistance to antiretroviral drug and whether it is related to VF. Methods:We analyzed the demographic, behavioral information, medical history, and drug resistance-associated mutation data from subjects. Drug resistance mutations at baseline and time of failure in patients suffering VF were detected by using the Vela automated next-generation sequencing platform. The x 2 test or Fisher exact test and logistic regression were used to assess the risk factors that contribute to VF in the potential drug-resistant people. Results:The prevalence of overall pretreatment drug resistance was 7.06% (233/3300), and the prevalence of pretreatment potential resistance was 8.79% (290/3300). All these patients with pretreatment potential first-line drugs resistance showed potential resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and some of them had potential drug resistance to NNRTIs and NRTIs or NNRTIs and PIs; among these patients, 94.71% (179/189) had V179 D/E mutations. The VF rate of first-line treatment for potentially resistant people is 17.99%. CD4 + T-cell count #200 cells/L at antiretroviral therapy initiation are risk factors for the failure of first-line treatment.Conclusions: The prevalence of potential drug resistance among individuals with HIV and the VF rate of first-line treatment for potential drug-resistant people were high. To better optimize clinical management, prevention, and control of HIV, attention should be devoted to the potential resistance of nonnucleoside drugs.

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Section: Discussion the Pretreatment Potential Resistance Of Nnrtis A...mentioning

confidence: 99%

The Effect of Pretreatment Potential Resistance to NNRTIs on Antiviral Therapy in Patients With HIV/AIDS

Xiao

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Quality management starts with intra-laboratory quality control. This is where laboratory information management systems are useful, i.e., software packages for effective monitoring and control of each step in the NGS-based HIV DR assay [35 ▪ ].…”

Section: Quality Assessment and Standardization Of Next-generation Se...mentioning

confidence: 99%

Technologies for HIV-1 drug resistance testing: inventory and needs

Metzner

2022

Current Opinion in HIV and AIDS

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Purpose of reviewHIV-1 drug resistance (HIV DR) testing is routinely performed by genotyping plasma viruses using Sanger population sequencing. Next-generation sequencing (NGS) is increasingly replacing standardized Sanger sequencing. This opens up new opportunities, but also brings challenges. Recent findingsThe number of NGS applications and protocols for HIV DR testing is increasing. All of them are noninferior to Sanger sequencing when comparing NGS-derived consensus sequences to Sanger sequencing-derived sequences. In addition, NGS enables high-throughput sequencing of near full-length HIV-1 genomes and detection of low-abundance drug-resistant HIV-1 variants, although their clinical implications need further investigation. Several groups have defined remaining challenges in implementing NGS protocols for HIV-1 resistance testing. Some of them are already being addressed. One of the most important needs is quality management and consequently, if possible, standardization.

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“…There is currently only one commercially available NGS assay approved by the FDA in November 2019 for clinical HIVDR genotyping, known as the Sentosa SQ HIV-1 Genotyping Assay [12,50]. This is a standardized, semi-automated and novel deep in vitro sequencing assay developed by Vela Diagnostics (Vela-Diagnostics, Humburg, Germany) for sequencing the combined HIV-1 PR, RT and integrase (IN) genes with minimal expertise [51].…”

Section: Sanger Sequencing and Ngs For Hivdr Genotypingmentioning

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

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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.

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Quality Control of Next-Generation Sequencing-Based HIV-1 Drug Resistance Data in Clinical Laboratory Information Systems Framework

Cited by 9 publications

References 46 publications

The Effect of Pretreatment Potential Resistance to NNRTIs on Antiviral Therapy in Patients With HIV/AIDS

The Effect of Pretreatment Potential Resistance to NNRTIs on Antiviral Therapy in Patients With HIV/AIDS

Technologies for HIV-1 drug resistance testing: inventory and needs

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

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