Randomized, Controlled Study of the Safety and Efficacy of Intravenous Cidofovir for the Treatment of Relapsing Cytomegalovirus Retinitis in Patients With AIDS

Abstract

To assess the effect of intravenous cidofovir on delaying progression of previously treated, relapsing cytomegalovirus (CMV) retinitis, we conducted a randomized, controlled comparison of two maintenance dose levels of cidofovir. One hundred and fifty patients with AIDS and CMV retinitis that had progressed or was persistently active despite treatment with ganciclovir, foscarnet, or both were randomized to receive induction cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with either 5 mg/kg or 3 mg/kg once every other week. Concomitant probenecid and intravenous hydration were administered with each cidofovir dose. Retinitis progression was assessed in the first 100 patients by bilateral, full-field retinal photographs read at a central reading center by an ophthalmologist masked to treatment assignment. Incidence of side effects, changes in visual acuity, and mortality were also assessed. Median time to retinitis progression as assessed by retinal photography was not reached (95% confidence interval [CI], 115 days-upper limit not reached) in the 5-mg/kg group, and was 49 days (95% CI, 35-52 days) in the 3-mg/kg group (p = .0006). Dose-dependent asymptomatic proteinuria (39%) and serum creatinine elevation (24%) were the most common adverse events thought to be related to cidofovir. Reversible probenecid reactions including constitutional symptoms and nausea occurred in 65 of 150 (43%) patients. Cidofovir therapy is effective in delaying progression of CMV retinitis that had previously progressed using other anti-CMV therapies.

Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients

“…Overall, renal toxicity developed in 25.6% of the patients; a proportion similar to that seen in AIDS patients given prophylactic hydration and probenecid. 2,3 This is encouraging since 72 of the 82 patients received additional nephrotoxic agents. More severe renal toxicity developed in 5 patients (2 of these developed renal failure and 3 significant tubulopathy).…”

“…5,17,26,27 CDV is a nucleotide analogue with broad antiviral activity, which has been shown to be effective against CMV retinitis refractory to other antiviral therapy in AIDS patients. [2][3][4] CDV has some attractive features for use in allogeneic SCT patients. Its therapeutic spectrum includes CMV, herpes simplex virus (including acyclovir-resistant strains), varicella-zoster virus, human herpesvirus 6, papovavirus, and adenovirus, all of which are recognized pathogens in allogeneic SCT recipients.…”

“…The risk for nephrotoxicity can be reduced, however, by the use of concomitant probenecid and prehydration. In 2 studies, Lalezari et al 2,3 reported 12% to 39% proteinuria and 24% increases in the serum creatinine despite these protective measures. Other important side effects reported from the studies in acquired immunodeficiency syndrome (AIDS) patients are bone marrow suppression and ophthalmologic toxicity.…”

“…It has advantages, such as a pharmacokinetic profile allowing once-a-week dosing, and studies have shown efficacy against CMV retinitis in human immunodeficiency virusinfected patients. [2][3][4] However, the toxicity profile of the drug, most importantly, nephrotoxicity, has limited its use in SCT recipients. The aim of this retrospective study was to collect information regarding efficacy and toxicity in allogeneic SCT patients treated with CDV.…”

Acute renal failure in a lung transplant patient after therapy with cidofovir

“…In patients treated with cidofovir, proteinuria and elevations in creatinine have been reported for 39 O/O and 24 % , respectively [5,6]. In addition, renal impairment was observed in some patients after cidofovir administration despite hydration with intravenous normal saline and the administration of oral probenecid to inhibit anion transport [7,4].…”