What is the evaluation approach for Cytomegalovirus (CMV) infection in adults?

From the Guidelines

Evaluation of CMV infection in adults should begin with a thorough clinical assessment and appropriate laboratory testing, prioritizing serology testing for CMV IgM and IgG antibodies and quantitative PCR for CMV DNA in blood for symptomatic patients, as recommended by the most recent guidelines 1. The evaluation process should consider the patient's immune status, as CMV infection is typically more severe in immunocompromised individuals. Key steps in the evaluation include:

• Serology testing for CMV IgM and IgG antibodies to determine if the infection is primary, reactivated, or past
• Quantitative PCR for CMV DNA in blood to assess viral load and disease activity in symptomatic patients
• Complete blood count to check for lymphocytosis or atypical lymphocytes
• Liver function tests to assess hepatic involvement
• Specific organ testing based on symptoms, such as bronchoscopy for pulmonary involvement In immunocompromised patients, more aggressive evaluation is warranted, including CMV viral load monitoring and possibly tissue biopsies from affected organs. Imaging studies such as chest X-ray or CT scan may be necessary depending on clinical presentation. Treatment decisions will depend on the severity of infection, immune status, and organ involvement, ranging from observation in immunocompetent patients with mild disease to antiviral therapy with ganciclovir, valganciclovir, foscarnet, or cidofovir in severe or immunocompromised cases, with oral letermovir being a viable option for prophylaxis in certain cases, as shown in recent studies 1. It is essential to consider the potential risks and benefits of different treatment options, including the risk of developing ganciclovir-resistant CMV and the cost of treatment, as highlighted in earlier guidelines 1.

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) [see Clinical Studies ( 14. 1)]. 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-]) [see Clinical Studies ( 14.1)].

The evaluation of CMV infection in adults involves:

• Treatment of CMV Retinitis: Valganciclovir is indicated for the treatment of CMV retinitis in patients with AIDS.
• Prevention of CMV Disease: Valganciclovir is indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk (D+/R-). According to the drug label 2 and 2.

From the Research

Evaluation of CMV Infection in Adults

• CMV infection in healthy adults is usually asymptomatic or causes a mild mononucleosis-like syndrome 3
• However, CMV disease can present with a wide range of manifestations, with colitis being the most common, and can cause significant morbidity and mortality in neonates and severely immunocompromised adults 3
• The incidence of severe CMV disease in immunocompetent adults appears to be greater than previously thought, which may be partly due to immune dysfunction related to comorbidities such as kidney disease or diabetes mellitus 3

Diagnosis and Treatment of CMV Infection

• Non-invasive testing for CMV is widely available and can facilitate early diagnosis if used appropriately 3
• Targeted antiviral therapy with ganciclovir or valganciclovir is appropriate for severe CMV disease in immunocompetent adults 3
• Valganciclovir is an orally administered prodrug of the standard anti-cytomegalovirus (CMV) drug 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 4
• The use of valganciclovir instead of intravenous ganciclovir may provide significant cost savings, based on data comparing oral versus intravenous regimens for the treatment of AIDS-related CMV retinitis 4

Pre-emptive Treatment for CMV Viraemia

• 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 probably reduces the risk of CMV disease compared with placebo or standard care, but may result in little or no difference in death (any cause) 5
• Compared to prophylaxis, pre-emptive treatment may make little or no difference to the risk of developing CMV disease and probably makes little or no difference to death (any cause) 5