What are the recommendations for CMV (Cytomegalovirus) testing and treatment?

From the Guidelines

CMV testing is recommended for immunocompromised patients, particularly those undergoing allogeneic HCT, with routine surveillance consisting of weekly monitoring by PCR, and treatment indicated for those with confirmed CMV viremia. Testing typically involves PCR blood tests to detect viral DNA, and treatment decisions should be guided by viral load monitoring. For treatment of active CMV infection, pre-emptive therapy with oral valganciclovir, intravenous ganciclovir, or intravenous foscarnet is recommended for at least 2 weeks and until CMV is no longer detectable 1. Alternative medications include intravenous foscarnet or intravenous cidofovir for ganciclovir-resistant cases, and oral maribavir for posttransplant CMV infection that is refractory to ganciclovir/valganciclovir, foscarnet, or cidofovir. Some key points to consider in CMV testing and treatment include:

• Surveillance should typically occur for at least 3 to 6 months posttransplant and during chronic GVHD requiring IST 1.
• Higher risk transplant subgroups may exist and require different management strategies.
• The benefits of long-term antiviral use must be weighed against the potential toxicity associated with it, such as bone marrow suppression, nephrotoxicity, and electrolyte abnormalities 1.
• A symptom-based approach to CMV testing, repeated testing to confirm whether CMV-DNA load is increasing, and appropriate diagnosis in case of suspected organ disease are warranted in patients with CLL receiving BCL-2 or BTK-inhibitors 1. In terms of prophylaxis, primary prophylaxis with oral or intravenous letermovir may be considered for CMV-seropositive recipients who undergo allogeneic HCT 1. However, the strategy of CMV surveillance testing by PCR followed by pre-emptive anti-CMV therapy for a positive result is favored over universal long-term prophylaxis. Regular monitoring of renal function, complete blood counts, and CMV viral loads is necessary to assess response and manage potential side effects.

From the FDA Drug Label

1 INDICATIONS & USAGE

1.1 Adult Patients Treatment of Cytomegalovirus (CMV) Retinitis: Valganciclovir tablets, USP are indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Prevention of CMV Disease: Valganciclovir tablets, USP are indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-])

The CMV testing recommendations are not explicitly stated in the provided drug labels. However, the labels do indicate that valganciclovir is used for the treatment and prevention of CMV disease in certain patient populations, such as those with AIDS or those who have received a transplant.

• The labels suggest that CMV disease prevention is recommended for kidney, heart, and kidney-pancreas transplant patients at high risk, which is defined as Donor CMV seropositive/Recipient CMV seronegative [D+/R-] 2.
• Additionally, CMV retinitis treatment is recommended for patients with acquired immunodeficiency syndrome (AIDS) 2.
• It is also indicated that valganciclovir is used for the prevention of CMV disease in heart transplant patients (4 months to 16 years of age) at high risk 2. The decision to perform CMV testing should be based on individual patient risk factors and clinical judgment.

From the Research

CMV Testing and Treatment Recommendations

• CMV (Cytomegalovirus) is a significant cause of morbidity and death in solid organ transplant recipients 3, 4, 5.
• The patients at highest risk of developing CMV disease are seronegative recipients of seropositive donors, and seropositive recipients who receive antilymphocyte agents such as OKT3 and antithymocyte globulin (ATG) for induction or for rejection 3.
• Sensitive tests that have been used for early diagnosis and monitoring of CMV are antigenemia and the polymerase chain reaction (PCR) 3.
• Antigen pp65 is a lower matrix protein and can be detected in peripheral blood leukocytes, with a sensitivity and specificity of 89% to 100% and 92% to 96%, respectively 3.
• Pre-emptive treatment of patients with CMV viraemia using antiviral agents has been suggested as an alternative to routine prophylaxis to prevent CMV disease 5.

Pre-emptive Treatment

• Pre-emptive treatment probably reduces the risk of CMV disease compared with placebo or standard care 5.
• There were no clear differences between pre-emptive treatment and prophylaxis to prevent CMV disease or reduce the risk of death (any cause) 5.
• The risk of CMV infection may be higher for patients receiving pre-emptive therapy, but the risk of adverse events, such as leucopenia, is probably lower 5.
• Oral valganciclovir (VGCV) has been used as preemptive therapy for CMV infection post allogeneic stem cell transplantation, with a complete clearance of the virus in all patients 6.

Treatment Options

• Ganciclovir is the most frequent antiviral agent used in transplant recipients and is usually well tolerated 3.
• Resistance to ganciclovir may occur and is usually secondary to virus mutation in the UL97 gene 3.
• Valganciclovir is an orally administered prodrug of ganciclovir, and is as effective as intravenous ganciclovir for the treatment of AIDS-related CMV retinitis, and oral ganciclovir for the prophylaxis of CMV infection and disease in high-risk solid organ transplant recipients 7.
• CMV hyperimmune globulin and leflunomide have been used to treat ganciclovir resistance CMV infection in cardiothoracic transplant recipients 4.