Comparison of Treatment Regimens for Cytomegalovirus Retinitis in Patients with AIDS in the Era of Highly Active Antiretroviral Therapy

Abstract

Purpose To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Design Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. Participants 250 patients with CMV retinitis and CD4+ T cells <100 cells/µL (n=221) at enrollment or incident retinitis (n=29) during cohort follow-up. Methods The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Main Outcome Measures Mortality, CMV dissemination, retinitis progression, treatment side effects. Results Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR]=0.5; 95% confidence interval [CI] = 0.3, 0.7; P=0.006), 90% reduction in new visceral CMV disease (adjusted HR=0.1; 95% CI = 0.04, 0.4;P=0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR=0.2; 95% CI= 0.1, 0.5; P=0.0005) when compared to those using only intraocular therapy (implants or injections). Compared to systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR=3.4, P=0.004) and greater visual field loss (for loss of ½ of the normal field, adjusted HR=5.5, P<0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression =0.5, P=0.26, and for loss ½ visual field =0.5, P=0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis among those treated with intravitreal injections was 0.017/EY (95% CI =0.006, 0.05) and among those treated with an implant 0.01/EY (95% CI =0.002, 0.04). Conclusions In the HAART era, systemic anti-CMV therapy, while there is immune compromise, appears to provide benefits in terms of longer survival and decreased CMV dissemination.

Cytomegalovirus retinitis and HIV: Case reviews from KwaZulu-Natal Province, South Africa

“…[3,26] This patient reported an onset of visual loss post ART initiation and could have been a case of missed CMV retinitis at screening as she was asymptomatic. An important consideration in this patient would be an immune reconstitution inflammatory syndrome presenting as an immune recovery vitritis or immune recovery uveitis (IRU).…”

“…[2] Despite antiretroviral therapy (ART), CMV infection in AIDS patients remains a significant risk factor for end organ disease and AIDS-related mortality. [3,4] Prior to the introduction of ART) 30 -40% of HIV-infected individuals developed CMV retinitis. [5] However, the introduction of ART has resulted in a precipitous decline in CMV retinitis infections, which is particularly evident in the developed world.…”

“…[21,22] Owing to its cost-effectiveness, intravitreal ganciclovir injection is the current standard treatment in the SA public sector for active CMV retinitis infection, [23] even though systemic ganciclovir or valganciclovir therapy is standard of care in other countries as these drugs assist in the prevention of systemic dissemination and improving survival. [3,23] These injections are prescribed in combination with daily ART; the dose is based on clinical response and immune recovery and is stopped when CD4+ cell counts of >100 cells/µL are achieved.[24] The third case developed retinal detachment, which is a severe complication of CMV retinitis. Risk factors for retinal detachment include large anterior retinal lesions, intravitreal ganciclovir injections and bilateral disease.…”

Cytomegalovirus retinitis in Cape Town, South Africa: Clinical management and outcomes

“…Intravitreal ganciclovir has been the mainstay of treatment for CMV retinits in South Africa (SA) and has been shown to have a better pharmacokinetic profile than intravitreal foscarnet, [7] although recent evidence [8] suggests that systemic treatment should be considered. Systemic treatment has a higher risk of side-effects than ocular treatment and has significant cost and resource implications.…”

Posterior Segment Drug Delivery Devices: Current and Novel Therapies in Development

“…12 However, more recent studies suggest that, in the era of highly active antiretroviral therapy, a ganciclovir implant device is less effective than systemic therapy at decreasing disease dissemination and improving patient survival. 13 Retisert. Retisert (Bausch & Lomb) is the first FDAapproved non-biodegradable sustained-release fluocinolone acetonide implant for the treatment of chronic noninfectious uveitis.…”