Alpha-interferon administration in cytomegalovirus retinitis

Abstract

Four patients, including three with the acquired immunodeficiency syndrome (AIDS), were treated with high-dose, buffy coat-derived alpha-interferon for progressive cytomegalovirus retinitis. Two of these patients had decreased viruria during therapy and the other two had increased viruria. There was evidence of progression of disease despite therapy in all patients, although the retinitis eventually became quiescent in the patient without AIDS. The severe immunosuppression encountered in AIDS patients complicates the management of cytomegalovirus and other opportunistic infections. CMV retinitis has become more commonly recognized as a complication of chronic CMV infection in immunosuppressed hosts, including those with the acquired immunodeficiency syndrome (AIDS) (5). Patients with CMV retinitis are good candidates for antivfral trials for several reasons. The disease tends to evolve less rapidly than some other CMV syndromes, thus allowing time for virological confirmation of the diagnosis before initiating therapy and time for a therapeutic effect to have an impact on the disease process. Because the eye lesions are characteristic and easily followed by objective criteria such as fundus photographs, clinical response may be readily assessed. Also, the risk of permanent visual loss and the lack of proven effective therapy has stimulated the use'of experimental antivirals in an effort to preserve vision.We report here our experience in the treatment of four patients with'CMV retinitis, using high-dose human leukocyte interferon. Three of the patients had AIDS. We monitored response clinically and virologically, using traditional tissue culture methods as well as the recently developed DNA hybridization assay for rapid measurement of viruria (3). diarrhea, perianal herpes simplex infection, and leukopenia. Two months before referral, visual loss in the left eye was noted, and a diagnosis of CMV retinitis was made. Viral culture of the urine showed CMV. Because of progression of lesions, a course of vidarabine was attempted, but this caused leukopenia and myalgias, and therapy was stopped after 2 weeks. Two weeks later, after resolution of the myalgias, interferon was begun at a dose of 5 x 106 U per day. Pretreatment urine culture showed 3.9 log TCID50 per 0.2 ml of CMV, with a positive DNA hybridization assay. A buffy coat culture was positive for CMV on day 2 of treatment. During therapy, granulocyte counts fell from 1,300/mm3 to a range of 700 to 1,000/mm3. The interferon dose was nevertheless increased to 5 x 106 U twice daily beginning 12 days after beginning therapy. This did not result in any further decrease of granulocyte counts; in fact, they rose to pretreatment levels. The patient experienced moderately severe anorexia and malaise, which appeared worse than that present before treatment. The increased interferon dosage was given for 26 days (for a total of 38 days of interferon). Four-hour post-injection interferon levels in the blood ranged from 80 U/ml at the lower dose to 225 U/ml at the higher d...

Treatment and Prophylaxis of Cytomegalovirus Disease

“…Ganciclovir is currently approved for the treatment of CMV retinitis. Foscarnet, a-interferon, and adenine arabinoside have been investigated for their effectiveness, but results obtained with ainterferon and adenine arabinoside have been 33…”

Effect of 2'-nor-cyclic GMP against guinea pig cytomegalovirus infection

“…Thus, antiviral agents against HCMV infection are urgently needed in light of the large spectrum of morbidity and mortality associated with the virus. The search for antiviral agents against this particular herpesvirus has resulted in limited success (1,6,22,24,29). Ganciclovir (also known as DHPG) has been shown to possess significant activity against HCMV in vitro and has been clinically used for the treatment of CMV infection in immunocompromised patients (5,7,(17)(18)(19)23).…”

Cytomegalovirus Retinitis in Rheumatic Disease: A Case Report

“…There has been 1 report of a patient who was treated with transfer factor and who had resolution of viremia and stabilization of retinitis (10). Four patients with CMV retinitis have been treated with interferon, without beneficial effect (11). Recently, there have been reports of improvement in CMV retinitis in AIDS patients treated with dihydroxy-2-propoxymethyl guanine (12,13).…”