Trial reportAntimicrobial agents and chemotherapy2008
Hepatotoxicity observed in clinical trials of aplaviroc (GW873140).
Trial report in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
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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
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review.Viruses · 2023Pooled it
- Efficacy and safety of maraviroc vs. efavirenz in treatment-naive patients with HIV-1: 5-year findings.AIDS (London, England) · 2014Trial
- Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial.Arthritis research & therapy · 2012Trial
- Two-year safety and virologic efficacy of maraviroc in treatment-experienced patients with CCR5-tropic HIV-1 infection: 96-week combined analysis of MOTIVATE 1 and 2.Journal of acquired immune deficiency syndromes (1999) · 2010Trial
- Virologic failure in first-line human immunodeficiency virus therapy with a CCR5 entry inhibitor, aplaviroc, plus a fixed-dose combination of lamivudine-zidovudine: nucleoside reverse transcriptase inhibitor resistance regardless of envelope tropism.Antimicrobial agents and chemotherapy · 2009Trial
- Maraviroc for previously treated patients with R5 HIV-1 infection.The New England journal of medicine · 2008Trial
- Hepatotoxicity observed in clinical trials of aplaviroc (GW873140).Antimicrobial agents and chemotherapy · 2008Trial
- Chemokines in the tumor microenvironment: implications for lung cancer and immunotherapy.Frontiers in immunology · 2024Review
- Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment.International journal of molecular sciences · 2022Review
- The Strategies and Challenges of CCR5 Gene Editing in Hematopoietic Stem and Progenitor Cells for the Treatment of HIV.Stem cell reviews and reports · 2021Review
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- Review
- Hepatotoxicity of Contemporary Antiretroviral Drugs: A Review and Evaluation of Published Clinical Data.Cells · 2021Review
- HIV-1 Entry and Prospects for Protecting against Infection.Microorganisms · 2021Review
- Innate Immune Response Against HIV-1.Advances in experimental medicine and biology · 2021Article
- Research Trends and Regulation of CCL5 in Prostate Cancer.OncoTargets and therapy · 2021Review
- [Homologous modeling and binding ability analysis of Spike protein after point mutation of severe acute respiratory syndrome coronavirus 2 to receptor proteins and potential antiviral drugs].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2020Article
- The G protein coupled receptor CCR5 in cancer.Advances in cancer research · 2020Review
- Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology.Cancer research · 2019Review
- CCR5 Inhibitors and HIV-1 Infection.Journal of AIDS and HIV treatment · 2019Article
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
No grant is acknowledged in the PubMed record.
Abstract
Aplaviroc (APL) was a new CCR5 antagonist that was investigated in two dose-ranging studies with antiretroviral therapy-naïve, human immunodeficiency virus-infected adults: ASCENT, in which 147 subjects were randomized 2:2:1 to receive zidovudine-lamivudine (ZDV-3TC) plus APL 600 mg twice a day (BID), APL 800 mg BID, or efavirenz (EFV), respectively, and EPIC, in which 195 subjects were randomized 2:2:2:1 to receive lopinavir-ritonavir (LPV-RTV) plus APL 200 mg BID, APL 400 mg BID, APL 800 mg once a day, or ZDV-3TC BID, respectively. Both studies (and, ultimately, the clinical development of APL) were discontinued after a mean of 14 weeks of therapy because of higher than anticipated severe liver toxicity; grade 2 or higher treatment-emergent elevations in alanine aminotransferase (ALT) levels were observed in 17/281 (6.0%) APL recipients but only 2/55 (3.6%) control recipients, while grade 2 or higher elevations in total bilirubin levels occurred in 29/281 (10.3%) APL recipients but only 4/55 (7.3%) controls. Two APL recipients developed grade 3 or higher treatment-emergent elevations in both ALT and total bilirubin levels, and one of these individuals had a severe case of hepatic cytolysis that was attributed to APL. Despite the high intersubject variability in APL plasma exposures, a Pearson correlation analysis of the combined study data did not reveal any significant associations between plasma concentrations and the liver enzyme elevations observed during the study. The mechanism for the idiosyncratic hepatotoxicity observed in the clinical trials of APL is unknown but is likely intrinsic to the molecule rather than its novel mechanism of action.
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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.