ArticleAntimicrobial agents and chemotherapy2015
Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Review
- Comprehensive database of HIV mutations selected during antiretroviral in vitro passage experiments.Antiviral research · 2024Article
- 2022 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2022Article
- Antiviral Activity and Resistance Profile of the Novel HIV-1 Non-Catalytic Site Integrase Inhibitor JTP-0157602.Journal of virology · 2022Article
- Specific mutations in the HIV-1 G-tract of the 3'-polypurine tract cause resistance to integrase strand transfer inhibitors.The Journal of antimicrobial chemotherapy · 2022Article
- Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals.International journal of environmental research and public health · 2021Article
- HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: a systematic review and meta-analysis protocol.Systematic reviews · 2020Article
- Article
- 2019 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2019Article
- Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence.Frontiers in microbiology · 2019Article
- Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors.Antimicrobial agents and chemotherapy · 2017Article
- HIV drug resistance against strand transfer integrase inhibitors.Retrovirology · 2017Review
- Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome.PloS one · 2017Article
- Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility.AIDS research and human retroviruses · 2016Article
- Review
- Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239.Journal of virology · 2015Article
- Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity.Journal of virology · 2015Article
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12 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The recently approved HIV-1 integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) (S/GSK1349572) has overall advantageous activity when tested in vitro against HIV-1 with raltegravir (RAL) and elvitegravir (EVG) resistance signature mutations. We conducted an in vitro resistance selection study using wild-type HIV-1 and mutants with the E92Q, Y143C, Y143R, Q148H, Q148K, Q148R, and N155H substitutions to assess the DTG in vitro barrier to resistance. No viral replication was observed at concentrations of ≥ 32 nM DTG, whereas viral replication was observed at 160 nM RAL or EVG in the mutants. In the Q148H, Q148K, or Q148R mutants, G140S/Q148H, E138K/Q148K, E138K/Q148R, and G140S/Q148R secondary mutations were identified with each INSTI and showed high resistance to RAL or EVG but limited resistance to DTG. E138K and G140S, as secondary substitutions to Q148H, Q148K, or Q148R, were associated with partial recovery in viral infectivity and/or INSTI resistance. In the E92Q, Y143C, Y143R, and N155H mutants, no secondary substitutions were associated with DTG. These in vitro results suggest that DTG has a high barrier to the development of resistance in the presence of RAL or EVG signature mutations other than Q148. One explanation for this high barrier to resistance is that no additional secondary substitution of E92Q, Y143C, Y143R, or N155H simultaneously increased the fold change in 50% effective concentration (EC50) to DTG and infectivity. Although increased DTG resistance via the Q148 pathway and secondary substitutions occurs at low concentrations, a higher starting concentration may reduce or eliminate the development of DTG resistance in this pathway in vitro.
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