A New Antiviral Option for Cytomegalovirus Prevention After Kidney Transplant

Raglow, Zoe; Kaul, Daniel

doi:10.1001/jama.2023.9100

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…Use of such traditional antivirals, including valganciclovir (VGCV) and ganciclovir (GCV), as prophylaxis has been primarily limited by bone marrow suppression [15,18,19]. This associated myelotoxicity often leads to earlier dose reduction or discontinuation of essential posttransplant immunosuppressive agents which could contribute to increased risk of graft rejection [20 ]. Head-tohead comparisons in randomized, clinical trials demonstrated significantly lower rates of myelosuppression with letermovir use (leukopenia: 11.3% vs. 37.0%, Dif -25.7, 95% CI -32.3, -19.1) compared to VGCV among kidney transplant recipients and similar rates (leukopenia: 2.9% vs. 3.6%, 95% CI -4.6, 2.2) to placebo when used in HSCT recipients [10,12 && ].…”

Section: Less Myelotoxicitymentioning

confidence: 99%

A new direction for cytomegalovirus prophylaxis among transplant recipients: Benefits and nonviral outcomes of letermovir use as primary CMV prophylaxis

Moore,

Boutin,

Tanna

2023

Current Opinion in Infectious Diseases

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Purpose of review Letermovir has changed the game of primary prophylaxis against cytomegalovirus (CMV) for hematopoietic stem cell transplant (HSCT) and more recently, solid organ transplant recipients. This is largely due to letermovir's similar efficacy in protecting against CMV reactivation and disease, along with its superior safety profile, notably reduced myelotoxicity, and lack of renal dose adjustment compared to standard agents like valganciclovir. This review will describe the potential benefits and clinical considerations of letermovir as prophylaxis among transplant recipients, with a focus on recent evidence describing nonviral outcomes of CMV. Recent findings Recent evidence has demonstrated improved safety (e.g., less myelosuppression) and tolerability with no difference in rates of CMV infection or disease in kidney transplant recipients given letermovir compared to valganciclovir. Real-world studies and meta-analyses in HSCT populations have explored various nonviral outcomes with letermovir use. Letermovir prophylaxis was associated with reduced mortality, lower rates of graft versus host disease, delayed CMV immune reconstitution, improved tolerability with extended durations, and decreased healthcare utilization. Summary Letermovir is an effective antiviral agent for CMV prevention and has demonstrated enhanced safety, which may allow for extended durations of primary prophylaxis among transplant recipients along with other improved clinical outcomes by mitigating the indirect effects of CMV.

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Section: Less Myelotoxicitymentioning

confidence: 99%

A new direction for cytomegalovirus prophylaxis among transplant recipients: Benefits and nonviral outcomes of letermovir use as primary CMV prophylaxis

Moore,

Boutin,

Tanna

2023

Current Opinion in Infectious Diseases

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“…Letermovir is highly specific for HCMV, as it has no activity against other herpesviruses or any other virus, and it is one of the most potent anti-HCMV agents identified to date, with reports illustrating up to 1000 times the potency of Ganciclovir [83]. It was approved in 2017 for HCMV prophylaxis in HCMV-seropositive adult hematopoietic cell transplant (HCT) recipients and has been widely adopted in this population, but it is currently not approved for any clinical indication in solid organ transplant recipients [84,85]. The approved dosage of Letermovir is 480 mg (240 mg if co-administered with cyclosporine) once daily.…”

Section: Antiviral Approach To Hcmv Infectionmentioning

confidence: 99%

Antiviral Approach to Cytomegalovirus Infection: An Overview of Conventional and Novel Strategies

Bottino,

Pastrone,

Curtoni

et al. 2023

Microorganisms

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Human cytomegalovirus (HCMV) is a herpesvirus capable of establishing a lifelong persistence in the host through a chronic state of infection and remains an essential global concern due to its distinct life cycle, mutations, and latency. It represents a life-threatening pathogen for immunocompromised patients, such as solid organ transplanted patients, HIV-positive individuals, and hematopoietic stem cell recipients. Multiple antiviral approaches are currently available and administered in order to prevent or manage viral infections in the early stages. However, limitations due to side effects and the onset of antidrug resistance are a hurdle to their efficacy, especially for long-term therapies. Novel antiviral molecules, together with innovative approaches (e.g., genetic editing and RNA interference) are currently in study, with promising results performed in vitro and in vivo. Since HCMV is a virus able to establish latent infection, with a consequential risk of reactivation, infection management could benefit from preventive treatment for critical patients, such as immunocompromised individuals and seronegative pregnant women. This review will provide an overview of conventional antiviral clinical approaches and their mechanisms of action. Additionally, an overview of proposed and developing new molecules is provided, including nucleic-acid-based therapies and immune-mediated approaches.

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Vaccines and Other Preventative Strategies for Immunocompromised Pneumonia

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2024

Clinics in Chest Medicine

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A New Antiviral Option for Cytomegalovirus Prevention After Kidney Transplant

Cited by 6 publications

References 20 publications

A new direction for cytomegalovirus prophylaxis among transplant recipients: Benefits and nonviral outcomes of letermovir use as primary CMV prophylaxis

A new direction for cytomegalovirus prophylaxis among transplant recipients: Benefits and nonviral outcomes of letermovir use as primary CMV prophylaxis

Antiviral Approach to Cytomegalovirus Infection: An Overview of Conventional and Novel Strategies

Vaccines and Other Preventative Strategies for Immunocompromised Pneumonia

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