ArticleThe Journal of infectious diseases2018
The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors.
Article in The Journal of infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- A systematic review of the genetic mechanisms of dolutegravir resistance.The Journal of antimicrobial chemotherapy · 2019Pooled it
- Predictors of virological failure in HIV-1-infected patients switching to dolutegravir maintenance monotherapy.HIV medicine · 2019Trial
- Cooperation between HIV-1 integrase natural polymorphism K156N and 3'PPT mutations in dolutegravir monotherapy failure.The Journal of antimicrobial chemotherapy · 2026Article
- Article
- The G118R plus R263K Combination of Integrase Mutations Associated with Dolutegravir-Based Treatment Failure Reduces HIV-1 Replicative Capacity and Integration.Antimicrobial agents and chemotherapy · 2023Article
- Structure of a HIV-1 IN-Allosteric inhibitor complex at 2.93 Å resolution: Routes to inhibitor optimization.PLoS pathogens · 2023Article
- Machine learning aided multiscale modelling of the HIV-1 infection in the presence of NRTI therapy.PeerJ · 2023Article
- Genotypic correlates of resistance to the HIV-1 strand transfer integrase inhibitor cabotegravir.Antiviral research · 2022Article
- HIV-1 Integrase Inhibitors with Modifications That Affect Their Potencies against Drug Resistant Integrase Mutants.ACS infectious diseases · 2021Article
- Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naïve individual case report.Medicine · 2020Article
- 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
- Structural basis of second-generation HIV integrase inhibitor action and viral resistance.Science (New York, N.Y.) · 2020Article
- A cross-sectional study to characterize local HIV-1 dynamics in Washington, DC using next-generation sequencing.Scientific reports · 2020Article
- Recent Advances in the Development of Integrase Inhibitors for HIV Treatment.Current HIV/AIDS reports · 2020Review
- Management of Virologic Failure and HIV Drug Resistance.Infectious disease clinics of North America · 2019Review
- Mutations in the HIV-1 envelope glycoprotein can broadly rescue blocks at multiple steps in the virus replication cycle.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Dolutegravir Monotherapy of Simian Immunodeficiency Virus-Infected Macaques Selects for Several Patterns of Resistance Mutations with Variable Virological Outcomes.Journal of virology · 2019Article
- Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence.Frontiers in microbiology · 2019Article
- Resistance to Dolutegravir-A Chink in the Armor?The Journal of infectious diseases · 2018Article
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Background: Dolutegravir (DTG) is an integrase strand-transfer inhibitor (INSTI) used for treatment of human immunodeficiency virus (HIV)-infected individuals. Owing to its high genetic barrier to resistance, DTG has been clinically investigated as maintenance monotherapy to maintain viral suppression and to reduce complication and healthcare costs. Our study aims to explain the underlying mechanism related to the emergence of a S230R substitution in patients who experienced virologic failure while using DTG monotherapy. Methods: We evaluated the effect of the S230R substitution in regard to integrase enzyme activity, viral infectivity, replicative capacity, and susceptibility to different INSTIs by biochemical and cell-based assays. Results: The S230R substitution conferred a 63% reduction in enzyme efficiency. S230R virus was 1.29-fold less infectious than wild-type virus but could replicate in PM1 cells without significant delay. Resistance levels against DTG, cabotegravir, raltegravir, and elvitegravir in tissue culture were 3.85-, 3.72-, 1.52-, and 1.21-fold, respectively, in virus with the S230R substitution. Conclusions: Our data indicate that the S230R substitution is comparable to the previously reported R263K substitution in some respects. Virologic failure during DTG monotherapy can occur through the development of the S230R or R263K mutation, without the need for high-level DTG resistance.
Indexed as
Identifiers
What OpenQuestion holds
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.