ArticlePloS one2012
Development of elvitegravir resistance and linkage of integrase inhibitor mutations with protease and reverse transcriptase resistance mutations.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 32 citations in OpenAlex.
- Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study.Antimicrobial agents and chemotherapy · 2022Trial
- Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study.The Journal of infectious diseases · 2013Trial
- Review
- Forgiveness of INSTI-Containing Regimens at Drug Concentrations Simulating Variable AdherenceAntimicrobial agents and chemotherapy · 2022Article
- Review
- Prevalence of integrase strand transfer inhibitor (INSTIs) resistance mutations in Henan Province, China (2018-2020).Infection · 2021Article
- Coevolved Multidrug-Resistant HIV-1 Protease and Reverse Transcriptase Influences Integrase Drug Susceptibility and Replication Fitness.Pathogens (Basel, Switzerland) · 2021Article
- Review
- Outcomes of Integrase Inhibitor-based Antiretroviral Therapy in a Clinical Cohort of Treatment-experienced Children, Adolescents and Young Adults With HIV Infection.The Pediatric infectious disease journal · 2020Observational
- Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy.International journal of molecular sciences · 2020Article
- Emergence of Integrase Resistance Mutations During Initial Therapy Containing Dolutegravir.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Article
- Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome.PloS one · 2017Article
- Response to Therapy in Antiretroviral Therapy-Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor-Associated Transmitted Drug Resistance.Journal of acquired immune deficiency syndromes (1999) · 2016Article
- Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions.Antimicrobial agents and chemotherapy · 2016Article
- Nonhuman Primates and Humanized Mice for Studies of HIV-1 Integrase Inhibitors: A Review.Pathogens & immunity · 2016Review
- Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239.Journal of virology · 2015Article
- In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2.Retrovirology · 2015Article
- Resistance analyses of integrase strand transfer inhibitors within phase 3 clinical trials of treatment-naive patients.Viruses · 2014Review
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Failure of antiretroviral regimens containing elvitegravir (EVG) and raltegravir (RAL) can result in the appearance of integrase inhibitor (INI) drug-resistance mutations (DRMs). While several INI DRMs have been identified, the evolution of EVG DRMs and the linkage of these DRMs with protease inhibitor (PI) and reverse transcriptase inhibitor (RTI) DRMs have not been studied at the clonal level. We examined the development of INI DRMs in 10 patients failing EVG-containing regimens over time, and the linkage of INI DRMs with PI and RTI DRMs in these patients plus 6 RAL-treated patients. A one-step RT-nested PCR protocol was used to generate a 2.7 kB amplicon that included the PR, RT, and IN coding region, and standard cloning and sequencing techniques were used to determine DRMs in 1,277 clones (mean 21 clones per time point). Results showed all patients had multiple PI, NRTI, and/or NNRTI DRMs at baseline, but no primary INI DRM. EVG-treated patients developed from 2 to 6 strains with different primary INI DRMs as early as 2 weeks after initiation of treatment, predominantly as single mutations. The prevalence of these strains fluctuated and new strains, and/or strains with new combinations of INI DRMs, developed over time. Final failure samples (weeks 14 to 48) typically showed a dominant strain with multiple mutations or N155H alone. Single N155H or multiple mutations were also observed in RAL-treated patients at virologic failure. All patient strains showed evidence of INI DRM co-located with single or multiple PI and/or RTI DRMs on the same viral strand. Our study shows that EVG treatment can select for a number of distinct INI-resistant strains whose prevalence fluctuates over time. Continued appearance of new INI DRMs after initial INI failure suggests a potent, highly dynamic selection of INI resistant strains that is unaffected by co-location with PI and RTI DRMs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.