High-dose (5000-μg) Intravitreal Ganciclovir Combined with Highly Active Antiretroviral Therapy for Cytomegalovirus Retinitis in HIV-Infected Patients in Venezuela

Abstract

Purpose

To describe the use of high doses of intravitreal ganciclovir combined with highly active antiretroviral therapy (HAART) for the treatment of cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients.

Methods

Thirteen HIV-infected patients (18 eyes) with active CMV retinitis (83.3% in zone 1 and 38.4% resistant) participated in this prospective interventional case series. Patients were treated with high dose intravitreal ganciclovir (5.0 mg/0.1 mL once a week) in combination with HAART therapy. Intravitreal injections were discontinued once CMV retinitis healed if there was a significant increase in CD4+ count (any increase of ≥50 cells/μL to levels over 100 cells/μL sustained for at least 3 months). Mean follow-up was 15.6 months. Main outcome measures included assessment of visual acuity and retinal inflammation (CMV retinitis activity). A matched historical control group of 20 eyes (15 patients) with CMV retinitis treated with systemic ganciclovir (intravenous [induction] and oral [maintenance]) was included.

Results

Complete regression of the retinitis was obtained with high doses of intravitreal ganciclovir in 88.8% of eyes (two patients died during follow-up) at a mean of 4.5 weeks (2 to 8 weeks). Visual acuity improved two or more lines in 61.1% of eyes. No ganciclovir retinal toxicity was identified. Three eyes presented CMV retinitis reactivation at a mean of 25.6 days after their last injection. Complications (33.3%) included retinal detachment (RD; 3 eyes), immune recovery uveitis (IRU; 2 eyes), and endophthalmitis (1 eye). In our control group complete regression of the retinitis was obtained in 100% of eyes at a mean of 4 weeks (3 to 7 weeks). However, 12 eyes (60%) presented with CMV retinitis relapse at a mean of 29 days (21 to 32 days) after initiating oral ganciclovir (maintenance). Complications included RD (7 eyes, 35%) and IRU (3 eyes, 15%). Severe neutropenia occurred in 2 patients (13%).

Conclusions

High doses of intravitreal ganciclovir (5.0 mg) once a week in combination with HAART therapy is effective to control CMV retinitis, and may be discontinued after CMV retinitis has healed if immune reconstitution with a significant increase in CD4+ count has occurred.