ArticleJournal of virology2009
Combinations of the first and next generations of human immunodeficiency virus (HIV) fusion inhibitors exhibit a highly potent synergistic effect against enfuvirtide- sensitive and -resistant HIV type 1 strains.
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 30 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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review.Viruses · 2023Pooled it
- Article
- ADS-J21 is a novel HIV-1 entry inhibitor targeting gp41.Current research in microbial sciences · 2024Article
- A Protein-Based, Long-Acting HIV-1 Fusion Inhibitor with an Improved Pharmacokinetic Profile.Pharmaceuticals (Basel, Switzerland) · 2022Article
- HIV-1 Entry and Membrane Fusion Inhibitors.Viruses · 2021Review
- HIV-1 fusion inhibitors targeting the membrane-proximal external region of Env spikes.Nature chemical biology · 2020Article
- Protein- and Peptide-Based Virus Inactivators: Inactivating Viruses Before Their Entry Into Cells.Frontiers in microbiology · 2020Review
- Synergistic inhibition of cell-to-cell HIV-1 infection by combinations of single chain variable fragments and fusion inhibitors.Biochemistry and biophysics reports · 2019Article
- Article
- Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41.Viruses · 2019Review
- Optimization of peptidic HIV-1 fusion inhibitor T20 by phage display.Protein science : a publication of the Protein Society · 2019Article
- Article
- Potent suppression of HIV-1 cell attachment by Kudzu root extract.Retrovirology · 2018Article
- Exceptional potency and structural basis of a T1249-derived lipopeptide fusion inhibitor against HIV-1, HIV-2, and simian immunodeficiency virus.The Journal of biological chemistry · 2018Article
- Enfuvirtide (T20)-Based Lipopeptide Is a Potent HIV-1 Cell Fusion Inhibitor: Implications for Viral Entry and Inhibition.Journal of virology · 2017Article
- Sustained release of the candidate antiretroviral peptides T-1249 and JNJ54310516-AFP from a rod insert vaginal ring.Drug delivery and translational research · 2016Article
- Prospects for Foamy Viral Vector Anti-HIV Gene Therapy.Biomedicines · 2016Review
- Nonneutralizing Antibodies Induced by the HIV-1 gp41 NHR Domain Gain Neutralizing Activity in the Presence of the HIV Fusion Inhibitor Enfuvirtide: a Potential Therapeutic Vaccine Strategy.Journal of virology · 2015Article
- Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein.Virus research · 2014Review
- Effect of amphipathic HIV fusion inhibitor peptides on POPC and POPC/cholesterol membrane properties: a molecular simulation study.International journal of molecular sciences · 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
5 authors at 2 institutions in 2 countries.
Funding
Abstract
T20 (generic name, enfuvirtide; brand name, Fuzeon) is a first-generation human immunodeficiency virus (HIV) fusion inhibitor approved for salvage therapy of HIV-infected patients refractory to current antiretroviral drugs. However, its clinical use is limited because of rapid emergence of T20-resistant viruses in T20-treated patients. Therefore, T1249 and T1144 are being developed as the second- and third-generation HIV fusion inhibitors, respectively, with improved efficacy and drug resistance profiles. Here, we found that combinations of T20 with T1249 and/or T1144 resulted in exceptionally potent synergism (combination index, <0.01) against HIV-1-mediated membrane fusion by 2 to 3 orders of magnitude in dose reduction. Highly potent synergistic antiviral efficacy was also achieved against infection by laboratory-adapted and primary HIV-1 strains, including T20-resistant variants. The mechanism underlying the synergistic effect could be attributed to the fact that T20, T1249, and T1144 all contain different functional domains and have different primary binding sites in gp41. As such, they may work cooperatively to inhibit gp41 six-helix bundle core formation, thereby suppressing virus-cell fusion. Therefore, these findings strongly imply that, rather than replacing T20, combining it with HIV fusion inhibitors of different generations might produce synergistic activity against both T20-sensitive and -resistant HIV-1 strains, suggesting a new therapeutic strategy for the treatment of HIV-1 infection/AIDS.
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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.