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Sections Cytomegalovirus (CMV)
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Medication

Medication Summary

The goals of pharmacotherapy are to prevent outbreaks of the disease and its complications and to reduce morbidity. Several agents are available for the treatment of cytomegalovirus (CMV) infection and disease.

In addition, multiple agents are being looked at for the treatment of CMV disease. These include (1) CMX001 (hexadecyloxypropyl-cidofovir, an ester of cidofovir), which is under development for ganciclovir-resistant CMV disease^[85]; (2) leflunomide, a pyrimidine synthesis inhibitor^[86](Leflunomide has been successfully used in solid organ transplant recipients for both CMV treatment and prophylaxis. Unfortunately, leflunomide failure has been reported in hematopoietic stem cell transplant recipients^[80]); and (3) artesunate, an antimalarial with some in vitro activity against CMV.^{[87, 88]}

Letermovir, a member of the novel class of 3,4-dihydroquinazolinyl acetic acids, is indicated for CMV prophylaxis in adult CMV-seropositive recipients of an allogeneic HSCT and kidney transplant recipients.^{[61, 63]}

Letermovir has also been studied for lung transplantation and was administered to a transplant recipient with multidrug-resistant disseminated CMV infection (viremia, pneumonitis, colitis, retinitis) in combination with reduced immunosuppression.^[89]The patient experienced rapid clinical, virologic, and radiographic resolution of disease.

Maribavir, a benzimidazole antiviral agent, has been used as salvage therapy in a small number of patients with multidrug-resistant CMV,^[74]but was unsuccessful when used as CMV prophylaxis in allogeneic stem cell transplant patients^[75]or in liver transplant recipients.

Class Summary

There are multiple antivirals with different mechanisms of action; these include DNA polymerase inhibitors like ganciclovir (nucleoside analog), cidofovir (nucleotide analog) as well as pyrophosphate analogues such as foscarnet. Ganciclovir is considered the treatment of choice for CMV infections.

Ganciclovir (Cytovene)

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Ganciclovir is a synthetic guanine derivative nucleoside analog active against CMV. It inhibits replication of herpes viruses both in vitro and in vivo. In patients with HIV infection, resistance manifests as progressive disease.

Foscarnet (Foscavir)

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Foscarnet inhibits viral replication of herpesviruses (CMV, HSV-1, HSV-2) at pyrophosphate-binding site on virus-specific DNA polymerases. It is used for ganciclovir-resistant CMV retinitis and herpes simplex disease.

Cidofovir (Vistide)

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Cidofovir is approved for the treatment of CMV retinitis in AIDS. It is a nucleotide analog, whose active metabolite inhibits herpes virus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerases alpha, beta, and gamma. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis.

Letermovir (Prevymis)

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Letermovir is part of a new class of non-nucleoside CMV inhibitors, the 3,4 dihydro-quinazoline-4-yl-acetic acid derivatives, and has activity in the late stages of viral replication rather than against the viral DNA polymerase like other anti-CMV therapies. Specifically, letermovir inhibits the viral terminase complex at pUL56 and pUL89, which leads to compromised viral replication by preventing genomes of proper unit length and the accumulation of immature viral DNA. Advantages of letermovir use include oral route and fewer side effects (no myelosupression, no nephrotoxicity).

It is indicated for prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT). Additionally, it is indicated for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (donor CMV seropositive/recipient CMV seronegative [D+/R-]).

Valganciclovir (Valcyte)

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Valganciclovir is an L-valyl ester prodrug of ganciclovir. It is used for CMV disease prophylaxis in various solid organ transplant recipients. It inhibits the replication of human CMV in vitro and in vivo. Valganciclovir achieves serum levels comparable to those obtained with IV ganciclovir.

Class Summary

Consists of administration of immunoglobulin pooled from serum of immunized subjects.

Cytomegalovirus immune globulin (CMV IG)

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CMV immune globulin (CMV-IG) is a preparation of immunoglobulin derived from pooled healthy blood donors with high CMV titers; administration provides a passive source of antibodies against cytomegalovirus. It is used for CMV pneumonia treatment. It may also be used for CMV prophylaxis in heart, lung, kidney, liver and pancreas transplant recipients, in addition to ganciclovir.

Class Summary

These agents inhibit cell growth and proliferation.

Leflunomide (Arava)

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Leflunomide has been used off-label in the treatment of cytomegalovirus (CMV) disease in transplant recipients, as well as in the prevention of acute and chronic rejection in recipients of solid organ transplants. It inhibits pyrimidine synthesis (via dihydroorotate dehydrogenase inhibition), leading to immunomodulatory and antiproliferative activity.

Questions

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Media Gallery

Here, using immunofluorescent technique, a specimen of human embryonic lung (25X) reveals the presence of cytomegalovirus. Courtesy of the CDC and Dr Craig Lyerla.
Hematoxylin-eosin–stained lung section showing typical owl-eye inclusions (480X). Courtesy of Danny L Wiedbrauk, PhD, Scientific Director, Virology & Molecular Biology, Warde Medical Laboratory, Ann Arbor, Michigan.

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Author

Ricardo Cedeno-Mendoza, MD Fellow in Infectious Diseases, Cooper University Hospital, Cooper Medical School of Rowan University

Ricardo Cedeno-Mendoza, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Lisa Vanchhawng Pedroza, MD Assistant Professor of Medicine, Attending Physician, Division of Infectious Diseases, Cooper University Hospital

Lisa Vanchhawng Pedroza, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John W King, MD Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University School of Medicine in Shreveport; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Todd S Wills, MD Associate Professor, Department of Medicine, Division of Infectious Disease and International Medicine, Program Director, Infectious Disease Fellowship Program, University of South Florida College of Medicine

Todd S Wills, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Kauser Akhter, MD Assistant Professor, Department of Internal Medicine, Florida State University College of Medicine; Associate Program Director, Infectious Diseases Fellowship Program, Orlando Health

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor Todd S Wills, MD to the development and writing of this article.

Sections Cytomegalovirus (CMV)
Overview
Presentation
- History
- Physical
- Causes
- Complications
- Show All
DDx
Workup
Treatment
Medication
Questions & Answers
Media Gallery
References

Cytomegalovirus (CMV) Medication

Medication Summary

Antivirals