Cytomegalovirus (CMV) is one of the most common opportunistic infections that affect the outcome of solid organ transplantation. This updated guideline from the American Society of Transplantation ...Infectious Diseases Community of Practice provides evidence‐based and expert recommendations for screening, diagnosis, prevention, and treatment of CMV in solid organ transplant recipients. CMV serology to detect immunoglobulin G remains as the standard method for pretransplant screening of donors and transplant candidates. Antiviral prophylaxis and preemptive therapy are the mainstays of CMV prevention. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is highlighted, as a result of variability of CMV nucleic acid testing, even in the contemporary era when calibrators are standardized. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management. Strategies for managing drug‐resistant CMV infection are presented. There is an increasing use of CMV‐specific cell‐mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, but their role in optimizing CMV prevention and treatment efforts has yet to be demonstrated. Specific issues related to pediatric transplant recipients are discussed.
Cytomegalovirus (CMV) is an opportunistic pathogen responsible for substantial morbidity after solid organ transplantation and haematopoietic stem cell transplantation. Treatment of CMV disease ...involves a two-pronged approach with antiviral drug treatment coupled with strategies to minimize the intensity of immune suppression.
This narrative review examines the evidence for the current treatment of CMV disease in transplant recipients, including the use of oral antiviral drugs.
Literature search was performed on PubMed with keywords cytomegalovirus, transplantation, ganciclovir, valganciclovir, maribavir, letermovir, cidofovir, and foscarnet.
Intravenous and oral valganciclovir are the standard first-line treatment of cytomegalovirus disease after transplantation. Oral maribavir has demonstrated superior efficacy and safety over CMV DNA polymerase inhibitors for the treatment of refractory or resistant CMV infection. Transplant patients with severe and life-threatening CMV disease, those with very high viral load, and patients with impaired gastrointestinal absorption should still be treated initially with intravenous antiviral drugs, including ganciclovir and foscarnet. Criteria for the safe transition from intravenous therapies to oral antiviral drugs include achieving clinical improvement and satisfactory decline in viral load. Recurrence of CMV viremia and disease is common, particularly among transplant patients who are lymphopenic and have impaired CMV-specific immunity.
Oral antiviral drugs for the treatment of CMV infection and disease in transplant recipients have improved the CMV landscape, because they reduce the cost and mitigate the inconvenience and risks related to prolonged hospitalization and the need for long-term intravascular access. However, their antiviral efficacy should be complemented by an intentional strategy of reducing the degree of immune suppression to allow for immunologic recovery that ensures durable control of CMV infection.
Cytomegalovirus (CMV) continues to be one of the most important pathogens that universally affect solid organ and allogeneic hematopoietic stem cell transplant recipients. Lack of effective ...CMV-specific immunity is the common factor that predisposes to the risk of CMV reactivation and clinical disease after transplantation. Antiviral drugs are the cornerstone for prevention and treatment of CMV infection and disease. Over the years, the CMV DNA polymerase inhibitor, ganciclovir (and valganciclovir), have served as the backbone for management, while foscarnet and cidofovir are reserved for the management of CMV infection that is refractory or resistant to ganciclovir treatment. In this review, we highlight the role of the newly approved drug, letermovir, a viral terminase inhibitor, for CMV prevention after allogeneic hematopoietic stem cell transplantation. Advances in immunologic monitoring may allow for an individualized approach to management of CMV after transplantation. Specifically, the potential role of CMV-specific T-cell measurements in guiding the need for the treatment of asymptomatic CMV infection and the duration of treatment of CMV disease is discussed. The role of adoptive immunotherapy, using ex vivo-generated CMV-specific T cells, is highlighted. This article provides a review of novel drugs, tests, and strategies in optimizing our current approaches to prevention and treatment of CMV in transplant recipients.
While the general population regained a certain level of normalcy with the end of the global health emergency, the risk of contracting COVID-19 with a severe outcome is still a major concern for ...people with compromised immunity. This paper reviews the impact of COVID-19 on people with immunocompromised status, identifies the gaps in the current management landscape, and proposes actions to address this unmet need. Observational studies have demonstrated that people with immune dysfunction have a higher risk of COVID-19-related hospitalization and death, despite vaccination, than the general population. More research is needed to define the optimal prevention and treatment strategies that are specific to people with immunocompromised status, including novel vaccination strategies, monoclonal antibodies that provide passive immunity and complement suboptimal vaccination responses, and improved and safer antiviral treatment for COVID-19. Preventive measures beyond vaccination alone are urgently needed to protect this vulnerable population.
Abstract Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available ...antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M2 protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M2 inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.
Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV ...infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.
Anti-spike monoclonal antibodies were highly effective for prophylaxis and early treatment of mild-to-moderate COVID-19 in high-risk populations.
This article reviews the clinical trials that led to ...the emergency use authorization of bamlanivimab with or without etesevimab, casirivimab and imdevimab, sotrovimab, bebtelovimab, and tixagevimab and cilgavimab in the United States. Clinical trials provided evidence that anti-spike monoclonal antibodies were highly effective, if administered early, for the treatment of mild-to-moderate COVID-19 among high-risk patients. Clinical trials also provided evidence that certain anti-spike monoclonal antibodies were highly effective when given as pre-exposure or post-exposure prophylaxis among high-risk individuals, including immunosuppressed populations. The evolution of SARS-CoV-2 resulted in spike mutations that conferred reduced susceptibility to anti-spike monoclonal antibodies.
Anti-spike monoclonal antibodies for treatment and prevention of COVID-19 resulted in therapeutic successes that resulted in reduced morbidity and improved survival among the high-risk populations. Lessons learned from their clinical use should guide the future development of durable antibody-based therapies. A strategy that will preserve their therapeutic lifespan is needed.
Cytomegalovirus (CMV) infection can be refractory to antiviral treatment. Although refractoriness can be due impaired host immunity, it can also be due to viral mutations that confer antiviral drug ...resistance. This article provides a succinct review of mutations in CMV genes that confer drug resistance, and offer guidance on clinical management.
Recent advances in medical and research technology have confirmed traditional mutations and identified novel ones that confer resistance to current antiviral drugs. Resistance to ganciclovir is commonly predicted by mutations in UL97, which encode for viral kinase that catalyzes its phosphorylation. Mutations in UL54, which encode for CMV DNA polymerase, confer resistance (or cross-resistance) to ganciclovir, cidofovir and/or foscarnet. Resistance to letermovir, the new drug approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients, has emerged and mapped most commonly to mutations in UL56 and less commonly UL51 and UL89, the gene complex that encode for viral terminase.
Mutations in CMV genes can be selected during antiviral drug exposure, and manifests phenotypically as nonresponsive drug-resistant disease. Knowledge of specific mutations informs clinicians in selecting appropriate antivirals for managing transplant patients with CMV disease.
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