ArticleJournal of virology2009
Non-cleavage site gag mutations in amprenavir-resistant human immunodeficiency virus type 1 (HIV-1) predispose HIV-1 to rapid acquisition of amprenavir resistance but delay development of resistance to other protease inhibitors.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 28 citations in OpenAlex.
- GRL-142 binds to and impairs HIV-1 integrase nuclear localization signal and potently suppresses highly INSTI-resistant HIV-1 variants.Science advances · 2023Article
- Viral proteases as therapeutic targets.Molecular aspects of medicine · 2022Review
- HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy.The Journal of antimicrobial chemotherapy · 2020Article
- A novel HIV-1 protease inhibitor, GRL-044, has potent activity against various HIV-1s with an extremely high genetic barrier to the emergence of HIV-1 drug resistance.Global health & medicine · 2019Article
- Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs.Molecules (Basel, Switzerland) · 2019Review
- Novel Protease Inhibitors Containing C-5-ModifiedAntimicrobial agents and chemotherapy · 2019Article
- GRL-079, a Novel HIV-1 Protease Inhibitor, Is Extremely Potent against Multidrug-Resistant HIV-1 Variants and Has a High Genetic Barrier against the Emergence of Resistant Variants.Antimicrobial agents and chemotherapy · 2018Article
- Article
- Article
- C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir.Journal of virology · 2015Article
- Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa.AIDS research and human retroviruses · 2015Article
- Deep sequencing of protease inhibitor resistant HIV patient isolates reveals patterns of correlated mutations in Gag and protease.PLoS computational biology · 2015Article
- HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir.The Journal of antimicrobial chemotherapy · 2015Article
- Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes.The Journal of antimicrobial chemotherapy · 2014Article
- Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1.Journal of virology · 2012Article
- Human Immunodeficiency Virus Gag and protease: partners in resistance.Retrovirology · 2012Review
- Loss of protease dimerization inhibition activity of darunavir is associated with the acquisition of resistance to darunavir by HIV-1.Journal of virology · 2011Article
- Single genome sequencing of HIV-1 gag and protease resistance mutations at virologic failure during the OK04 trial of simplified versus standard maintenance therapy.Antiviral therapy · 2011Article
- Positive selection pressure introduces secondary mutations at Gag cleavage sites in human immunodeficiency virus type 1 harboring major protease resistance mutations.Journal of virology · 2009Article
- Pre-steady-state kinetics of interaction of wild-type and multiple drug-resistant HIV protease with first and second generation inhibitory drugs.Doklady. Biochemistry and biophysicsArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
In an attempt to determine whether mutations in Gag in human immunodeficiency virus type 1 (HIV-1) variants selected with a protease inhibitor (PI) affect the development of resistance to the same or a different PI(s), we generated multiple infectious HIV-1 clones carrying mutated Gag and/or mutated protease proteins that were identified in amprenavir (APV)-selected HIV-1 variants and examined their virological characteristics. In an HIV-1 preparation selected with APV (33 passages, yielding HIV(APVp33)), we identified six mutations in protease and six apparently critical mutations at cleavage and non-cleavage sites in Gag. An infectious recombinant clone carrying the six protease mutations but no Gag mutations failed to replicate, indicating that the Gag mutations were required for the replication of HIV(APVp33). An infectious recombinant clone that carried wild-type protease and a set of five Gag mutations (rHIV(WTpro)(12/75/219/390/409gag)) replicated comparably to wild-type HIV-1; however, when exposed to APV, rHIV(WTpro)(12/75/219/390/409gag) rapidly acquired APV resistance. In contrast, the five Gag mutations significantly delayed the acquisition of HIV-1 resistance to ritonavir and nelfinavir (NFV). Recombinant HIV-1 clones containing NFV resistance-associated mutations, such as D30N and N88S, had increased susceptibilities to APV, suggesting that antiretroviral regimens including both APV and NFV may bring about favorable antiviral efficacy. The present data suggest that the preexistence of certain Gag mutations related to PI resistance can accelerate the emergence of resistance to the PI and delay the acquisition of HIV resistance to other PIs, and these findings should have clinical relevance in the therapy of HIV-1 infection with PI-including regimens.
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.