A 28-year-old immunocompromised patient (CD4 count 45 cells/µL) with HIV presents with retinitis and floaters. Fundoscopy shows a granular, hemorrhagic lesion with indistinct borders in the peripheral retina. CMV retinitis is suspected. What is the drug of choice for induction therapy?

Explanation

## Drug of Choice for CMV Retinitis Induction Therapy **Key Point:** Ganciclovir is the first-line induction agent for CMV retinitis in severely immunocompromised patients, administered either IV or via intravitreal injection. ### Pathophysiology of CMV Retinitis CMV retinitis occurs almost exclusively when CD4 count falls below **50 cells/µL**. The virus causes a granular, hemorrhagic, "cottage cheese and ketchup" appearance with indistinct borders, progressing centripetally if untreated. ### Ganciclovir: Mechanism & Rationale **Mechanism:** 1. Nucleoside analogue requiring viral protein kinase (UL97) for activation 2. Inhibits CMV DNA polymerase with high selectivity 3. Achieves high intracellular concentrations in infected cells **Induction Regimen:** - **IV ganciclovir:** 5 mg/kg IV twice daily for 14–21 days - **Intravitreal ganciclovir:** 2 mg in 0.05 mL injected directly into vitreous (preferred for peripheral lesions or when IV access problematic) - **Ganciclovir implant:** Sustained-release device; alternative for central lesions ### Comparative Antiviral Therapy for CMV Retinitis | Agent | Route | Induction Dose | Maintenance | Toxicity | First-Line? | |-------|-------|----------------|-------------|----------|-------------| | **Ganciclovir** | IV or intravitreal | 5 mg/kg BD × 14–21 d | 5 mg/kg daily | Myelosuppression, nephrotoxicity (mild) | ✓ Yes | | **Foscarnet** | IV | 60 mg/kg TDS × 14–21 d | 90–120 mg/kg daily | Severe nephrotoxicity, electrolyte disturbances, seizures | Alternative | | **Cidofovir** | IV | 5 mg/kg weekly × 2 weeks | 5 mg/kg every 2 weeks | Severe nephrotoxicity (requires hydration + probenecid) | Salvage only | | **Acyclovir** | IV | 10–15 mg/kg TDS | — | Neurotoxicity at high doses | **NOT effective** for CMV | **High-Yield:** Ganciclovir is preferred because it has the best efficacy-to-toxicity ratio for CMV retinitis. Foscarnet is reserved for ganciclovir-resistant strains (UL97 mutants) or when myelosuppression is intolerable. Cidofovir is a salvage agent due to severe nephrotoxicity. ### Clinical Pearl **Immune Recovery Uveitis (IRU):** After immune reconstitution with antiretroviral therapy (CD4 >100 cells/µL), patients may develop paradoxical inflammation in the eye (IRU), which can be managed with topical or systemic corticosteroids. This does not require stopping antiviral therapy. ### Why Intravitreal Route? Intravitreal ganciclovir or implant is often preferred because: - Direct delivery to site of infection - Avoids systemic toxicity - Effective for peripheral lesions - Reduces systemic drug burden ### Maintenance Therapy After induction, **maintenance therapy** with ganciclovir 5 mg/kg IV daily (or intravitreal injections monthly) is mandatory to prevent relapse until CD4 count recovers to >100 cells/µL on antiretroviral therapy. [cite:Harrison 21e Ch 187]