ArticlePloS one2013
Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics.
Article in PloS one, 2013. 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.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Effects of Low- and High-Mineral Content Water on the Relative Bioavailability of a Coformulated Abacavir/Dolutegravir/Lamivudine Dispersible Tablet in Healthy Adults.Journal of acquired immune deficiency syndromes (1999) · 2018Trial
- Dolutegravir developmental toxicity is mitigated by magnesium and folate in zebrafish embryos.Disease models & mechanisms · 2026Article
- Brief Histories of Retroviral Integration Research and Associated International Conferences.Viruses · 2024Review
- Efficacy, safety, and tolerability of dolutegravir-based ART regimen in Durban, South Africa: a cohort study.BMC infectious diseases · 2024Article
- Comorbidity and concomitant medication use in an integrase strand transfer inhibitor naïve cohort on first-line dolutegravir-based antiretroviral therapy.The Pan African medical journal · 2024Article
- A computational overview of integrase strand transfer inhibitors (INSTIs) against emerging and evolving drug-resistant HIV-1 integrase mutants.Archives of microbiology · 2023Review
- A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection.Retrovirology · 2022Review
- 2022 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2022Article
- HIV-1 Reverse Transcriptase/Integrase Dual Inhibitors: A Review of Recent Advances and Structure-activity Relationship Studies.Iranian journal of pharmaceutical research : IJPR · 2021Review
- Evidence for Disruption of MgFrontiers in molecular biosciences · 2020Article
- Review
- Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition.The Journal of biological chemistry · 2019Review
- 2019 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2019Article
- Evaluation of Anti-HIV-1 Integrase and Anti-Inflammatory Activities of Compounds fromAdvances in pharmacological sciences · 2019Article
- Article
- 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
- Different Pathways Leading to Integrase Inhibitors Resistance.Frontiers in microbiology · 2016Review
- Multifunctional facets of retrovirus integrase.World journal of biological chemistry · 2015Review
- Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro.Antimicrobial agents and chemotherapy · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signature HIV-1 integrase mutations associated with clinical raltegravir resistance involve 1 of 3 primary genetic pathways, Y143C/R, Q148H/K/R and N155H, the latter 2 of which confer cross-resistance to elvitegravir. In accord with clinical findings, in vitro drug resistance profiling studies with wild-type and site-directed integrase mutant viruses have shown significant fold increases in raltegravir and elvitegravir resistance for the specified viral mutants relative to wild-type HIV-1. Dolutegravir, in contrast, has demonstrated clinical efficacy in subjects failing raltegravir therapy due to integrase mutations at Y143, Q148 or N155, which is consistent with its distinct in vitro resistance profile as dolutegravir's antiviral activity against these viral mutants is equivalent to its activity against wild-type HIV-1. Kinetic studies of inhibitor dissociation from wild-type and mutant integrase-viral DNA complexes have shown that dolutegravir also has a distinct off-rate profile with dissociative half-lives substantially longer than those of raltegravir and elvitegravir, suggesting that dolutegravir's prolonged binding may be an important contributing factor to its distinct resistance profile. To provide a structural rationale for these observations, we constructed several molecular models of wild-type and clinically relevant mutant HIV-1 integrase enzymes in complex with viral DNA and dolutegravir, raltegravir or elvitegravir. Here, we discuss our structural models and the posited effects that the integrase mutations and the structural and electronic properties of the integrase inhibitors may have on the catalytic pocket and inhibitor binding and, consequently, on antiviral potency in vitro and in the clinic.
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.