What is the appropriate treatment for a patient with a systemic viral infection, considering their demographic and medical history?

Treatment of Systemic Viral Infection

For serious systemic viral infections, particularly cytomegalovirus (CMV) disease, intravenous ganciclovir 5 mg/kg twice daily for 14-21 days is the mandatory first-line treatment, with transition to oral valganciclovir 900 mg twice daily after clinical improvement for less severe cases. 1

Initial Assessment and Disease Severity Classification

When evaluating a patient with suspected systemic viral infection, immediately determine:

• Specific viral pathogen through PCR testing, antigen detection, or tissue biopsy with histopathology 1, 2
• Immune status including HIV status with CD4+ count, transplant status, or other immunosuppressive conditions 1, 2
• Organ involvement to classify as serious disease (retinitis, pneumonitis, gastrointestinal disease with severe symptoms, encephalitis, disseminated infection) versus mild disease 1

Treatment Algorithm by Viral Pathogen

Cytomegalovirus (CMV) Disease

Serious CMV Disease (Retinitis, Pneumonitis, Encephalitis, Disseminated Infection):

• Initiate IV ganciclovir 5 mg/kg twice daily immediately for 14-21 days as mandatory initial therapy 1
• For CMV encephalitis specifically, use combination therapy: ganciclovir 5 mg/kg IV every 12 hours PLUS foscarnet 60 mg/kg IV every 8 hours (or 90 mg/kg every 12 hours) for 3 weeks to maximize response 1
• Continue treatment until CMV is no longer detectable by PCR or antigenemia assay 3, 1
• Reduce or discontinue immunosuppressive medications whenever clinically feasible, as this decreases mortality and improves outcomes 3, 1

Less Severe CMV Disease:

• Oral valganciclovir 900 mg twice daily is adequate for mild disease without life-threatening complications 1
• Transition from IV to oral therapy after clinical improvement (typically 3-5 days) if gastrointestinal absorption is assured 2

CMV Retinitis Specific Approach:

• For sight-threatening lesions: Ganciclovir intraocular implant PLUS oral valganciclovir 900 mg twice daily is superior to systemic therapy alone 4
• For small peripheral lesions: Oral valganciclovir 900 mg twice daily alone is adequate 4
• Consider initial intravitreous ganciclovir injection at diagnosis for immediate high local drug concentration 4

Alternative Agents for Ganciclovir Resistance or Intolerance:

• Foscarnet 60 mg/kg IV every 8 hours for 14-21 days, administered slowly over 2 hours with saline fluid loading to minimize nephrotoxicity 1
• IV cidofovir as third-line option, though it carries substantial nephrotoxicity risk 4

Herpes Simplex Virus (HSV) Infections

Superficial HSV 1,2 Infection:

• Oral acyclovir, valacyclovir, or famciclovir until all lesions resolve 3

Systemic HSV 1,2 Infection:

• IV acyclovir immediately with reduction in immunosuppressive medications 3
• Continue IV acyclovir until clinical response, then switch to oral antiviral agent (acyclovir, valacyclovir, or famciclovir) to complete 14-21 days total 3

HSV Blepharoconjunctivitis:

• Topical trifluridine or topical ganciclovir (less toxic to ocular surface) PLUS oral antivirals 3
• Oral acyclovir 250 mg twice daily, or higher doses if resistance suspected 3
• Avoid topical corticosteroids as they potentiate HSV epithelial infections 3

Varicella Zoster Virus (VZV) Infections

Primary VZV (Chicken Pox) in Transplant Recipients:

• IV or oral acyclovir, continued at least until all lesions have scabbed 3

Uncomplicated Herpes Zoster (Shingles):

• Oral acyclovir 800 mg five times daily for 7 days OR valacyclovir 1000 mg every 8 hours for 7 days OR famciclovir 500 mg three times daily for 7 days 3
• Continue at least until all lesions have scabbed 3

Disseminated or Invasive Herpes Zoster:

• IV acyclovir immediately with temporary reduction in immunosuppressive medications 3
• Continue at least until all lesions have scabbed 3

VZV Conjunctivitis:

• Oral antivirals at doses above (acyclovir 800 mg five times daily, valacyclovir 1000 mg every 8 hours, or famciclovir 500 mg three times daily) 3
• Topical antivirals alone are not helpful but may be used as additive treatment in unresponsive patients 3

Hepatitis B Virus (HBV) in Cancer Patients

Chronic HBV (HBsAg-positive) Receiving Anticancer Therapy:

• Preemptive antiviral prophylaxis with entecavir (preferred), tenofovir disoproxil fumarate, or tenofovir alafenamide 3
• Start before anticancer therapy and continue for minimum 12 months after completion (18 months for rituximab-based regimens or hematopoietic stem-cell transplantation) 3
• Avoid lamivudine due to resistance 3

Past HBV Infection (Anti-HBc Positive, HBsAg Negative) with High-Risk Therapy:

• Antiviral prophylaxis during and for minimum 12 months after anti-CD20 monoclonal antibodies or stem-cell transplantation 3
• Alternative: Monitor with HBsAg and ALT every 3 months during therapy and up to 6 months after, starting preemptive therapy immediately if HBsAg or HBV DNA becomes positive 3

Hepatitis C Virus (HCV) in Transplant Recipients

• Antiviral treatment only when benefits clearly outweigh rejection risk (e.g., fibrosing cholestatic hepatitis, life-threatening vasculitis) 3
• Standard interferon monotherapy if treatment necessary 3

Influenza

Eligible Patients (Acute Influenza-Like Illness with Fever >38°C, Symptomatic ≤2 Days):

• Oseltamivir 75 mg every 12 hours for 5 days 3
• Reduce dose by 50% (75 mg once daily) if creatinine clearance <30 mL/minute 3

Exceptions to Fever Requirement:

• Immunocompromised or very elderly patients unable to mount adequate febrile response may still receive treatment 3

Hospitalized Severely Ill Patients:

• May benefit from antiviral treatment started >48 hours from onset, particularly if immunocompromised, despite lack of evidence 3

Critical Monitoring Requirements

During CMV Treatment

Laboratory Monitoring:

• Complete blood count twice weekly during induction phase (first 14-21 days) due to high risk of neutropenia, anemia, thrombocytopenia 1, 4
• Weekly CBC during maintenance phase 4
• Serum creatinine and electrolytes twice weekly during induction, then weekly 1, 4
• CMV viral load by PCR weekly to assess treatment response 3, 1

Clinical Monitoring:

• Temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation at least twice daily 3
• For CMV retinitis: dilated indirect ophthalmoscopy at diagnosis, after induction completion, at 1 month, then monthly while on treatment 4

During HSV/VZV Treatment

• Follow-up visit within 1 week consisting of interval history, visual acuity measurement, and slit-lamp biomicroscopy for ocular involvement 3

During HBV Prophylaxis

• Monitor viral load with PCR monthly through treatment and every 3 months after completion 3
• Baseline HBV DNA prior to or at beginning of anticancer therapy, then every 6 months during antiviral therapy 3

Maintenance and Long-Term Management

CMV Disease

• After successful induction, maintenance therapy with valganciclovir 900 mg once daily 1, 5
• In HIV-infected patients: continue lifelong until immune reconstitution (CD4+ >100 cells/µL sustained for 3-6 months) 1, 4
• In transplant patients: continue for at least 12 months after discontinuation of immunosuppressive therapy 3

HSV with Frequent Recurrences

• Prophylactic antiviral agent (acyclovir, valacyclovir, or famciclovir) for patients experiencing frequent recurrences 3

HBV After Cancer Treatment

• Surveillance for at least 6-12 months after conclusion of antiviral treatment 3
• Coordination with hepatologist for long-term management 3

Concurrent Immunotherapy

For HIV-Infected Patients:

• Initiate or optimize antiretroviral therapy (ART) concurrently with CMV treatment in all HIV-infected patients 1, 2

For Transplant Recipients:

• Reduce immunosuppression if clinically feasible during active viral disease 3, 1, 2
• Monitor graft function closely during viral disease 3

Major Toxicities and Management

Ganciclovir/Valganciclovir

• Myelosuppression (dose-limiting): Occurs in up to 40% of patients—severe neutropenia, anemia, thrombocytopenia 1, 4, 5
• Nephrotoxicity: Occurs in up to 30%—monitor creatinine closely and adjust doses for renal impairment 1
• Electrolyte abnormalities: Occur in approximately one-third—can cause seizures or cardiac dysrhythmias 1
• Nausea, diarrhea 4

Foscarnet

• Nephrotoxicity: Dose-related—requires aggressive hydration and slow infusion 1, 4
• Electrolyte abnormalities: Hypocalcemia, hypomagnesemia, hypokalemia 4
• Neurologic dysfunction: Including seizures 2, 4

Cidofovir

• Severe nephrotoxicity: Dose-related and potentially irreversible 4
• Ocular hypotony 4
• Contraindicated in renal dysfunction or proteinuria 4

Acyclovir/Valacyclovir

• Renal dysfunction with rapid IV administration—ensure adequate hydration 3
• Neurologic effects at high doses in renal impairment 3

Common Pitfalls to Avoid

• Do not delay antiviral therapy in serious systemic viral infections while awaiting confirmatory testing—initiate empirically based on clinical presentation 1
• Do not use topical corticosteroids in HSV epithelial infections as they potentiate viral replication 3
• Do not use lamivudine for HBV prophylaxis due to high resistance rates—use entecavir or tenofovir 3
• Do not stop CMV treatment based on clinical improvement alone—continue until viral clearance documented by PCR 3, 1
• Do not use topical antivirals alone for VZV conjunctivitis—they are ineffective without systemic therapy 3
• Do not administer foscarnet rapidly—infuse over 2 hours with saline loading to prevent nephrotoxicity 1