What is the recommended treatment regimen for cytomegalovirus disease in a patient with AIDS?

Treatment of Cytomegalovirus Disease in AIDS Patients

For AIDS patients with CMV disease, initiate induction therapy with intravenous ganciclovir 5 mg/kg every 12 hours for 14-21 days, followed by lifelong maintenance therapy with oral valganciclovir 900 mg once daily, as CMV disease cannot be cured with currently available antivirals. 1, 2, 3

Initial Induction Therapy

Standard CMV Retinitis (Non-Sight-Threatening)

• Administer IV ganciclovir 5 mg/kg every 12 hours for 14-21 days, infusing each dose slowly over 1-2 hours to minimize acute toxicity 1, 3
• Alternatively, oral valganciclovir 900 mg twice daily for 14-21 days may be used for peripheral retinal lesions not immediately threatening vision, as it provides equivalent systemic exposure to IV ganciclovir 4, 3
• Never infuse ganciclovir faster than the recommended 1-2 hour duration to avoid neuromuscular blockade and acute toxicity 3

Sight-Threatening Lesions (Adjacent to Optic Nerve or Fovea)

• 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 14-21 days 2, 3
• This combination achieves improvement or stabilization in 74% of patients with severe CMV disease 3

CMV Encephalitis or Other End-Organ Disease

• Combination therapy is mandatory: ganciclovir 5 mg/kg IV every 12 hours PLUS foscarnet 60 mg/kg IV every 8 hours for at least 3 weeks, as monotherapy frequently fails 2, 3
• For CMV colitis or esophagitis, IV ganciclovir 5 mg/kg twice daily for 3-5 days followed by oral valganciclovir 900 mg twice daily for 2-3 weeks until symptoms resolve 5

Lifelong Maintenance (Secondary Prophylaxis)

CMV disease is never cured with current antivirals; therefore, chronic suppressive therapy must continue for life unless immune reconstitution occurs. 1, 2

Preferred Maintenance Regimens

• Oral valganciclovir 900 mg once daily (preferred due to superior bioavailability and ease of administration) 4, 3
• IV ganciclovir 5 mg/kg once daily (5-7 days per week) if oral therapy is not tolerated 1, 2
• For retinitis specifically: ganciclovir intraocular implant PLUS oral ganciclovir (the implant alone does not protect the contralateral eye or other organs) 1, 2

Alternative Maintenance Options

• Parenteral foscarnet for ganciclovir-resistant CMV or intolerance 1, 2
• Parenteral cidofovir as third-line agent 1, 2
• Combined ganciclovir plus foscarnet for resistant disease 1

Critical Monitoring Requirements

Hematologic Surveillance

• Monitor complete blood count and platelets twice weekly during induction and once weekly during maintenance 3
• Myelosuppression (neutropenia, anemia, thrombocytopenia) is the major dose-limiting toxicity, requiring dose reduction or interruption in up to 40% of patients 3
• Consider granulocyte colony-stimulating factor (G-CSF) for severe neutropenia 3

Renal Function Monitoring

• Check serum creatinine at least weekly during induction and regularly during maintenance 3
• Ensure adequate hydration before and during infusions to mitigate nephrotoxicity 3

Ophthalmologic Follow-Up (for Retinitis)

• Dilated indirect ophthalmoscopy at diagnosis, after induction, at 1 month, then monthly while on therapy to detect disease progression 3
• Even patients with immune recovery (CD4+ >100 cells/µL) can experience retinitis relapse at rates of 0.03/person-year, so continued monitoring is essential 1

Dose Adjustments for Renal Impairment

Induction Dosing Adjustments (IV Ganciclovir)

• CrCl 50-69 mL/min: 2.5 mg/kg every 24 hours 3
• CrCl 25-49 mL/min: 1.25 mg/kg every 24 hours 3
• CrCl 10-24 mL/min: 0.625 mg/kg every 24 hours 3
• CrCl <10 mL/min or hemodialysis: 0.625 mg/kg three times weekly after each dialysis session 3

Maintenance Dosing Adjustments (Valganciclovir)

• CrCl 40-59 mL/min: 450 mg once daily 3, 4
• CrCl 25-39 mL/min: 450 mg every 48 hours 3, 4
• CrCl 10-24 mL/min: 450 mg twice weekly 3, 4
• CrCl <10 mL/min or dialysis: Valganciclovir is not recommended; use IV ganciclovir with appropriate adjustments 3, 4

When to Discontinue Maintenance Therapy

Maintenance therapy may be discontinued only when immune reconstitution is achieved and sustained. 1, 2

Criteria for Safe Discontinuation

• CD4+ count sustained >100-150 cells/µL for at least 3-6 months on effective antiretroviral therapy 1, 2
• HIV plasma RNA levels suppressed on HAART 1
• Decision must be made in consultation with an ophthalmologist for retinitis cases, considering lesion location, vision in contralateral eye, and feasibility of regular monitoring 1, 2

When to Restart Maintenance

• Restart prophylaxis if CD4+ count decreases to <50-100 cells/µL 1

Common Pitfalls and How to Avoid Them

Do Not Shorten Induction Duration

• Never reduce induction below 14 days, as this increases risk of early disease progression and treatment failure 3

Do Not Use Oral Therapy for Severe Disease

• Oral valganciclovir should not be used in patients with severe gastrointestinal symptoms that impair absorption; use IV therapy instead 3

Do Not Discontinue Maintenance Prematurely

• Even when retinitis appears stable, cessation without immune reconstitution leads to rapid progression within 6-8 weeks 1

Avoid Acyclovir and Valacyclovir for CMV

• Acyclovir is ineffective for CMV disease 1
• Valacyclovir is contraindicated due to unexplained increased mortality in AIDS patients when used for CMV prophylaxis 1

Drug Resistance Considerations

• Extended ganciclovir use increases risk of developing ganciclovir-resistant CMV strains 1, 2, 6
• When resistance is suspected (in vitro IC₅₀ >3 µg/mL), switch to foscarnet or use combination ganciclovir plus foscarnet 3
• Cidofovir may be considered as third-line therapy for resistant infections 1, 2

Role of Antiretroviral Therapy

• Initiate or optimize HAART alongside CMV treatment, as immune reconstitution is the most effective long-term strategy for controlling CMV disease 5, 7
• The incidence of new CMV disease has declined by 75-80% since the advent of effective antiretroviral therapy 1
• HAART has dramatically reduced CMV-related mortality in AIDS patients 7, 8

Primary Prophylaxis (Not Routinely Recommended)

• Oral ganciclovir prophylaxis may be considered for CMV-seropositive patients with CD4+ <50 cells/µL, but this is a weak recommendation 1, 2
• Routine prophylaxis is generally not advised due to ganciclovir-induced neutropenia, anemia, conflicting efficacy data, lack of proven survival benefit, risk of resistance, and cost 1, 2
• The most important prevention method is early recognition of disease: educate patients to report increased floaters and assess visual acuity regularly by reading newsprint 1