ArticleThe Journal of infectious diseases2012
Study of genotypic and phenotypic HIV-1 dynamics of integrase mutations during raltegravir treatment: a refined analysis by ultra-deep 454 pyrosequencing.
Article in The Journal of infectious diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy.PloS one · 2014Trial
- A bibliometric analysis of HIV-1 drug-resistant minority variants from 1999 to 2024.AIDS research and therapy · 2025Article
- 2022 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2022Article
- Recent Advances in the Development of Integrase Inhibitors for HIV Treatment.Current HIV/AIDS reports · 2020Review
- 2019 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2019Article
- The Role of HIV-1 Drug-Resistant Minority Variants in Treatment Failure.The Journal of infectious diseases · 2017Review
- Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome.PloS one · 2017Article
- Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors.PloS one · 2017Article
- Evaluation of the dynamic pattern of viral evolution in patients with virological breakthrough during treatment with nucleoside/nucleotide analogs by ultra‑deep pyrosequencing.Molecular medicine reports · 2016Article
- Retroviral integration: Site matters: Mechanisms and consequences of retroviral integration site selection.BioEssays : news and reviews in molecular, cellular and developmental biology · 2015Review
- Dengue Virus Evolution under a Host-Targeted Antiviral.Journal of virology · 2015Article
- Article
- Deep sequencing: becoming a critical tool in clinical virology.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2014Review
- Targeted deep sequencing of HIV-1 using the IonTorrentPGM platform.Journal of virological methods · 2014Article
- Next-Generation Sequencing to Help Monitor Patients Infected with HIV: Ready for Clinical Use?Current infectious disease reports · 2014Article
- Sensitive deep-sequencing-based HIV-1 genotyping assay to simultaneously determine susceptibility to protease, reverse transcriptase, integrase, and maturation inhibitors, as well as HIV-1 coreceptor tropism.Antimicrobial agents and chemotherapy · 2014Article
- Stable HIV-1 integrase diversity during initial HIV-1 RNA decay suggests complete blockade of plasma HIV-1 replication by effective raltegravir-containing salvage therapy.Virology journal · 2013Article
- Comparison of pyrosequencing, Sanger sequencing, and melting curve analysis for detection of low-frequency macrolide-resistant mycoplasma pneumoniae quasispecies in respiratory specimens.Journal of clinical microbiology · 2013Article
- Clinical implications of HIV-1 minority variants.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2013Article
Corrections and comments
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe dynamics of raltegravir-resistant variants and their impact on virologic response in 23 HIV-1-infected patients, who started a salvage raltegravir-containing regimen, were investigated.
methodsIntegrase population sequencing and Ultra-Deep-454 Pyrosequencing (UDPS) were performed on plasma samples at baseline and at raltegravir failure. All integrase mutations detected at a frequency ≥1% were considered to be reliable for the UDPS analyses. Phylogenetic and phenotypic resistance analyses were also performed.
resultsAt baseline, primary resistance mutations were not detected by both population and UDPS genotypic assays; few secondary mutations (T97A-V151I-G163R) were rarely detected and did not show any statistically association either with virologic response at 24-weeks or with the development of resistant variants at failure. At UDPS, not all resistant variants appearing early during treatment evolved as major populations during failure; only specific resistance pathways (Y143R-Q148H/R-N155H) associated with an increased rate of fitness and phenotypic resistance were selected.
conclusionsResistance to raltegravir in integrase strand transfer inhibitor-naive patients remains today a rare event, which might be changed by future extensive use of such drugs. In our study, pathways of resistance at failure were not predicted by baseline mutations, suggesting that evolution plus stochastic selection plays a major role in the appearance of integrase-resistance mutations, whereas fitness and resistance are dominant factors acting for the late selection of resistant quasispecies.
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