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Viruses
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Human Cytomegalovirus Therapeutic Strategies and Clinical Applications
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Human Cytomegalovirus Therapeutic Strategies and Clinical Applications

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 1785

Special Issue Editor

Dr. Ravit Arav-Boger

E-Mail Website
Guest Editor
Department of Pediatrics, Division of Infectious Disease, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Interests: human cytomegalovirus; cytomegalovirus; infection; molecular virology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and a major pathogen that impacts morbidity, mortality, and cost of care after transplantation. Perhaps no other virus has such diverse consequences, affecting pregnancies, child health, and transplant outcomes. Despite its critical impact on human health, treatment options for HCMV are limited. The nucleoside analog ganciclovir (GCV) and its oral formulation val-GCV improved outcomes for transplantation, and val-GCV may prevent hearing deterioration in congenitally infected children. However, prolonged courses of therapy result in intolerable toxicities to the bone marrow and selection for resistant viruses. The alternative drugs for GCV-resistant HCMV, foscarnet, and cidofovir, also target the viral DNA polymerase; both are nephrotoxic and can only be administered intravenously. New agents include the terminase inhibitor letermovir, FDA-approved for HCMV prophylaxis after bone marrow transplantation, and the viral UL97 kinase inhibitor, maribavir, approved for refractory HCMV disease in adults and children >12 years. Given the emergence of resistance to all agents, there is a great need for additional treatment options for HCMV, including new therapeutic strategies. In this Special Issue, we will focus on recent advances in therapeutic strategies for HCMV and specific treatment considerations for patients at risk for CMV disease.

Dr. Ravit Arav-Boger
Guest Editor

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Keywords

  • human cytomegalovirus (HCMV)
  • congenital infection
  • transplantation
  • side effects
  • resistance
  • therapeutic strategies
  • combination therapy

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Published Papers (2 papers)

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8 pages, 169 KB  
Communication
Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients
by Steven B. Kleiboeker
Viruses 2025, 17(3), 421; https://doi.org/10.3390/v17030421 - 14 Mar 2025
Viewed by 1181
Abstract
Background: Human cytomegalovirus (CMV) remains an important pathogen, especially for immunocompromised patients such as solid organ and hematopoietic stem cell recipients. Viral genomic mutations conferring drug resistance are an important impediment to effective CMV management and frequently lead to use of alternative antiviral [...] Read more.
Background: Human cytomegalovirus (CMV) remains an important pathogen, especially for immunocompromised patients such as solid organ and hematopoietic stem cell recipients. Viral genomic mutations conferring drug resistance are an important impediment to effective CMV management and frequently lead to use of alternative antiviral drugs to treat CMV disease. Methods: Results from 1459 de-identified patient samples with both UL54 and UL97 sequencing results were analyzed for ganciclovir (GCV) and maribavir (MBV) resistance mutations. Genomic sequencing was performed by the Sanger method and resistance mutations were identified by comparison to CMV reference strain AD169. Results: Ganciclovir resistance was identified in 379 of 1459 (25.98%) of the samples tested, with most resistance-conferring mutations present in viral gene UL97. A total of 121 of 1459 (8.29%) samples had MBV resistance mutations, and 84 (69.42%) of the 121 samples with MBV resistance also had GCV resistance mutations. Of the 84 samples with resistance to both MBV and GCV, 35 (41.67%) had a single UL97 mutation conferring resistance to both drugs, either C480F or F342Y. The overall prevalence of C480F was increased relative to an earlier analysis of samples from this reference laboratory. Conclusions: Although a high prevalence of CMV resistance mutations was identified, this must be taken in the context of healthcare providers submitting samples from patients with suspected CMV resistance. Most MBV-resistant samples were also resistant to GCV, suggesting that use of MBV as an alternative to GCV may benefit from genotypic resistance testing to achieve the effective control of CMV disease. Full article
(This article belongs to the Special Issue Human Cytomegalovirus Therapeutic Strategies and Clinical Applications)
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11 pages, 1097 KB  
Case Report
Refractory CMV Enteritis in Small Bowel Transplantation: A Case Highlighting the Challenges of Balancing Immunosuppression and Novel Antiviral Therapies
by Abdulrahman A. Al-Saud, Ehab H. Abufarhaneh, Madain S. Alsanea, Reem M. Alameer, Amani H. Yamani, Fatimah S. Alhamlan and Reem S. Almaghrabi
Viruses 2025, 17(10), 1379; https://doi.org/10.3390/v17101379 - 15 Oct 2025
Abstract
Background: Cytomegalovirus (CMV) remains a formidable complication in small bowel transplantation (SBT) due to the graft’s high immunogenicity and profound immunosuppression required, with refractory disease representing a particularly devastating challenge. Case: We report an 18-year-old male who underwent SBT, complicated by recurrent acute [...] Read more.
Background: Cytomegalovirus (CMV) remains a formidable complication in small bowel transplantation (SBT) due to the graft’s high immunogenicity and profound immunosuppression required, with refractory disease representing a particularly devastating challenge. Case: We report an 18-year-old male who underwent SBT, complicated by recurrent acute rejection episodes requiring intensive immunosuppression. He developed refractory CMV disease, marked by non-response to first line therapy with ganciclovir—despite the absence of genotypic resistance—necessitating sequential use of foscarnet, dual antivirals, CMV immunoglobulin, and novel agents (maribavir and letermovir). Discussion: This case illustrates the multifactorial drivers of refractory CMV disease in SBT recipients, including donor–recipient serostatus mismatch, profound immunosuppression through T-cell-depleting induction, corticosteroid exposure, and biologic therapy. It highlights the distinction between refractory and resistant CMV, and the role of combination antiviral strategies including novel agents to achieve disease control. Outcomes remain dismal despite aggressive and innovative therapies, underscoring the limited efficacy of interventions in the context of severe immunologic compromise. Conclusions: Refractory CMV enteritis in SBT exemplifies the extreme difficulty of balancing viral control with rejection management. Despite exhausting antiviral strategies, survival remains poor. Highlights: Refractory CMV enteritis is a significant challenge in small bowel transplant recipients due to intense immunosuppression. Persistent CMV disease may occur despite antiviral prophylaxis and the absence of resistant gene mutations. Combination antiviral strategies, including maribavir, demonstrated significant clinical improvement. Profound immunosuppression required to manage acute graft rejection episodes complicates antiviral management and disease clearance. Despite best efforts in CMV management in this population, outcomes may still be compromised by unrelated or compounding factors. Full article
(This article belongs to the Special Issue Human Cytomegalovirus Therapeutic Strategies and Clinical Applications)
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