Trial reportPloS one2011
Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461.
Trial report in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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
32 citing papers in PubMed, 77 citations in OpenAlex.
- Trial
- Quasispecies Nature of RNA Viruses: Lessons from the Past.Vaccines · 2023Review
- Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity.Viruses · 2022Review
- Structural Insights Into Tautomeric Dynamics in Nucleic Acids and in Antiviral Nucleoside Analogs.Frontiers in molecular biosciences · 2021Review
- Synergistic lethal mutagenesis of hepatitis C virus.Antimicrobial agents and chemotherapy · 2019Article
- Quasispecies and virus.European biophysics journal : EBJ · 2018Review
- Persistence of SIV in the brain of SIV-infected Chinese rhesus macaques with or without antiretroviral therapy.Journal of neurovirology · 2018Article
- Lethal mutagenesis of an RNA plant virus via lethal defection.Scientific reports · 2018Article
- Rare haplotype load as marker for lethal mutagenesis.PloS one · 2018Article
- Antiviral drug resistance as an adaptive process.Virus evolution · 2016Review
- Lack of mutational hot spots during decitabine-mediated HIV-1 mutagenesis.Antimicrobial agents and chemotherapy · 2015Article
- Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Evaluation of anti-HIV-1 mutagenic nucleoside analogues.The Journal of biological chemistry · 2015Article
- Novel inhibitors of human immunodeficiency virus type 2 infectivity.The Journal of general virology · 2014Article
- Review
- Article
- Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2'-deoxycytidine.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Probing the molecular mechanism of action of the HIV-1 reverse transcriptase inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) using pre-steady-state kinetics.Antiviral research · 2014Article
- Loss and recovery of genetic diversity in adapting populations of HIV.PLoS genetics · 2014Article
- 5,6-Dihydro-5-aza-2'-deoxycytidine potentiates the anti-HIV-1 activity of ribonucleotide reductase inhibitors.Bioorganic & medicinal chemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first "mechanism validation" phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.
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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.