ArticleJournal of virology2012
Deep sequencing reveals minor protease resistance mutations in patients failing a protease inhibitor regimen.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed.
- Randomized trial of stopping or continuing ART among postpartum women with pre-ART CD4 ≥ 400 cells/mm3.PloS one · 2017Trial
- Improved Detection of HIV-1 Drug Resistance With Droplet Digital Polymerase Chain Reaction: A Comparative Study and Its Implications.Open forum infectious diseases · 2025Article
- Full-spectrum HIV drug resistance mutation detection by high-resolution complete pol gene sequencing.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2023Article
- Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa.BMC infectious diseases · 2021Article
- Limited Marginal Utility of Deep Sequencing for HIV Drug Resistance Testing in the Age of Integrase Inhibitors.Journal of clinical microbiology · 2018Article
- HIV-1 second-line failure and drug resistance at high-level and low-level viremia in Western Kenya.AIDS (London, England) · 2018Article
- Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay.AIDS research and therapy · 2018Article
- Laboratory Methods in Molecular Epidemiology: Viral Infections.Microbiology spectrum · 2018Review
- Sanger and Next Generation Sequencing Approaches to Evaluate HIV-1 Virus in Blood Compartments.International journal of environmental research and public health · 2018Article
- Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations.Nature reviews. Genetics · 2018Review
- Seasonal Genetic Drift of Human Influenza A Virus Quasispecies Revealed by Deep Sequencing.Frontiers in microbiology · 2018Article
- Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis.The Pan African medical journal · 2018Article
- Evaluation of different analysis pipelines for the detection of HIV-1 minority resistant variants.PloS one · 2018Article
- The Role of HIV-1 Drug-Resistant Minority Variants in Treatment Failure.The Journal of infectious diseases · 2017Review
- Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014.Journal of the International AIDS Society · 2017Article
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- Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors.PloS one · 2017Article
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- The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility.Retrovirology · 2016Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Standard genotypic antiretroviral resistance testing, performed by bulk sequencing, does not readily detect variants that comprise <20% of the circulating HIV-1 RNA population. Nevertheless, it is valuable in selecting an antiretroviral regimen after antiretroviral failure. In patients with poor adherence, resistant variants may not reach this threshold. Therefore, deep sequencing would be potentially valuable for detecting minority resistant variants. We compared bulk sequencing and deep sequencing to detect HIV-1 drug resistance at the time of a second-line protease inhibitor (PI)-based antiretroviral regimen failure. Eligibility criteria were virologic failure (HIV-1 RNA load of >500 copies/ml) of a first-line nonnucleoside reverse transcriptase inhibitor-based regimen, with at least the M184V mutation (lamivudine resistance), and second-line failure of a lopinavir/ritonavir (LPV/r)-based regimen. An amplicon-sequencing approach on the Roche 454 system was used. Six patients with viral loads of >90,000 copies/ml and one patient with a viral load of 520 copies/ml were included. Mutations not detectable by bulk sequencing during first- and second-line failure were detected by deep sequencing during second-line failure. Low-frequency variants (>0.5% of the sequence population) harboring major protease inhibitor resistance mutations were found in 5 of 7 patients despite poor adherence to the LPV/r-based regimen. In patients with intermittent adherence to a boosted PI regimen, deep sequencing may detect minority PI-resistant variants, which likely represent early events in resistance selection. In patients with poor or intermittent adherence, there may be low evolutionary impetus for such variants to reach fixation, explaining the low prevalence of PI resistance.
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