When should we treat adenovirus (adenoviral) infection in the blood?

Treatment of Adenovirus Infection in Blood

Treatment with cidofovir should be initiated in severely ill immunocompromised patients with adenovirus detected in blood, particularly those with evidence of disseminated disease or significant symptoms. 1

Patient Risk Stratification

Adenovirus infections in the blood require a risk-based approach to treatment:

High-Risk Patients (Require Treatment)

• Patients with impaired cellular immunity (transplant recipients, especially bone marrow/HSCT)
• Patients with evidence of disseminated disease
• Severely symptomatic patients
• Patients with rising viral loads on serial monitoring

Moderate-Risk Patients (Consider Treatment)

• Immunocompromised patients with detectable adenovirus in blood but minimal symptoms
• Patients with stable or low viral loads

Low-Risk Patients (Observation)

• Immunocompetent patients with incidental finding of adenovirus in blood
• Patients with declining viral loads without treatment

Treatment Algorithm

1. Confirm diagnosis: Verify adenovirus detection in blood via PCR or culture
2. Assess immune status: Determine degree of immunocompromise
3. Evaluate for dissemination: Check for multi-organ involvement (respiratory, GI, urinary tract)
4. Monitor viral load: Quantitative PCR to establish baseline and trend
5. Initiate treatment for high-risk patients or those with evidence of disease progression

Treatment Options

First-Line Treatment

• Cidofovir: 5 mg/kg IV once weekly for 2 weeks, then once every other week 1
  • Must be given with probenecid to reduce nephrotoxicity
  • Monitor renal function closely due to significant nephrotoxicity

Alternative Options

• Low-dose cidofovir: 1 mg/kg three times weekly (for patients with renal concerns) 1
• Brincidofovir: Lipid ester of cidofovir with less nephrotoxicity (when available) 2
• Ribavirin: Limited evidence of efficacy, but may be considered when cidofovir is contraindicated 3

Monitoring During Treatment

• Weekly quantitative viral load monitoring
• A significant drop (>1 log) in viral load indicates good response 2
• Monitor renal function, electrolytes, and complete blood count
• Continue treatment until viral clearance or significant clinical improvement

Special Considerations

• Pediatric patients: May require dose adjustments; consider ribavirin as an alternative 3
• Renal impairment: Use low-dose cidofovir regimen with careful monitoring
• Pregnancy: Risk-benefit assessment needed as cidofovir is potentially teratogenic

Treatment Endpoints

• Continue treatment until:
  • Resolution of clinical symptoms
  • Negative PCR for adenovirus in blood on two consecutive tests
  • At least 2-3 weeks of treatment completed for severe cases

Common Pitfalls

• Delayed treatment initiation: Early treatment is associated with better outcomes; don't wait for severe symptoms in high-risk patients
• Inadequate monitoring: Failure to monitor viral loads may miss treatment failure
• Nephrotoxicity: Failure to provide adequate hydration and probenecid with cidofovir
• Premature discontinuation: Stopping treatment before adequate viral clearance can lead to relapse

The evidence for treatment of adenovirus in blood is largely based on case reports and small case series rather than randomized controlled trials. However, given the high mortality rate (up to 80%) in immunocompromised patients with disseminated disease 3, 4, early intervention with cidofovir is warranted in high-risk patients despite potential toxicities.