ArticleAntimicrobial agents and chemotherapy2015
In vitro drug combination studies of Letermovir (AIC246, MK-8228) with approved anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV and HIV replication.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- The HCMV terminase as an antiviral target: structural insights, inhibitory mechanisms, and the era of letermovir.Frontiers in microbiology · 2026Review
- Drug interactions in people with HIV treated with antivirals for other viral illnesses.Expert opinion on drug metabolism & toxicology · 2025Review
- Recent advances in human cytomegalovirus: a comprehensive review of pathogenic mechanisms, virus-host interactions, and antiviral strategies.Frontiers in immunology · 2025Review
- Exploring the Potential of HIV Integrase Inhibitors as Therapeutic Agents Against HSV and HCMV: A Molecular Docking Study.Journal of experimental pharmacology · 2025Article
- Management of Cytomegalovirus Infections in the Era of the Novel Antiviral Players, Letermovir and Maribavir.Infectious disease reports · 2024Review
- Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers.Pharmaceutics · 2023Article
- In vitro assessment of the combined effect of letermovir and sirolimus on cytomegalovirus replication.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2023Article
- Anti-CMV therapy, what next? A systematic review.Frontiers in microbiology · 2023Review
- Cytomegalovirus antiviral stewardship in the COVID-19 Era: Increasing complexity of prophylaxis and treatment and potential mitigation strategies.Transplant infectious disease : an official journal of the Transplantation Society · 2021Review
- Evaluation of Small Molecule Combinations against Respiratory Syncytial Virus In Vitro.Molecules (Basel, Switzerland) · 2021Article
- Combinatorial Drug Treatments Reveal Promising Anticytomegaloviral Profiles for Clinically Relevant Pharmaceutical Kinase Inhibitors (PKIs).International journal of molecular sciences · 2021Article
- Antiviral Drugs Against Herpesviruses.Advances in experimental medicine and biology · 2021Article
- Review
- The Cytomegalovirus Protein Kinase pUL97:Host Interactions, Regulatory Mechanisms and Antiviral Drug Targeting.Microorganisms · 2020Review
- Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy.Current hematologic malignancy reports · 2020Review
- Synergism of PARP inhibitor fluzoparib (HS10160) and MET inhibitor HS10241 in breast and ovarian cancer cells.American journal of cancer research · 2019Article
- Letermovir for the prevention of cytomegalovirus infection and disease in transplant recipients: an evidence-based review.Infection and drug resistance · 2019Review
- Human Cytomegalovirus Latency and Reactivation in Allogeneic Hematopoietic Stem Cell Transplant Recipients.Frontiers in microbiology · 2019Review
- Antiviral activity of maribavir in combination with other drugs active against human cytomegalovirus.Antiviral research · 2018Article
- Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation.Blood advances · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite modern prevention and treatment strategies, human cytomegalovirus (HCMV) remains a common opportunistic pathogen associated with serious morbidity and mortality in immunocompromised individuals, such as transplant recipients and AIDS patients. All drugs currently licensed for the treatment of HCMV infection target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Letermovir (AIC246, MK-8228) is a new anti-HCMV agent in clinical development that acts via a novel mode of action and has demonstrated anti-HCMV activity in vitro and in vivo. For the future, drug combination therapies, including letermovir, might be indicated under special medical conditions, such as the emergence of multidrug-resistant virus strains in transplant recipients or in HCMV-HIV-coinfected patients. Accordingly, knowledge of the compatibility of letermovir with other HCMV or HIV antivirals is of medical importance. Here, we evaluated the inhibition of HCMV replication by letermovir in combination with all currently approved HCMV antivirals using cell culture checkerboard assays. In addition, the effects of letermovir on the antiviral activities of selected HIV drugs, and vice versa, were analyzed. Using two different mathematical techniques to analyze the experimental data, (i) additive effects were observed for the combination of letermovir with anti-HCMV drugs and (ii) no interaction was found between letermovir and anti-HIV drugs. Since none of the tested drug combinations significantly antagonized letermovir efficacy (or vice versa), our findings suggest that letermovir may offer the potential for combination therapy with the tested HCMV and HIV drugs.
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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.