The Effect of Cidofovir on Cytomegalovirus-Induced Hearing Loss in a Guinea Pig Model

Abstract

To evaluate the utility of therapy with the cyclic cogener of the anti-cytomegalovirus (CMV) agent cidofovir against CMV-induced hearing loss in a guinea pig model. Thirty-six guinea pigs were randomly divided into 4 groups of 9. All groups underwent auditory brainstem response testing on days 0, 4, 7, 14, 21, and 28. Group 1 received no intervention. Group 2 underwent sham surgery consisting of unilateral round window injection of 25 microL of sterile viral media on day 0. Groups 3 and 4 underwent round window injection of 1.7 x 10(5) plaque-forming units of guinea pig CMV on day 0. Group 4 received antiviral treatment with intraperitoneal injection of cidofovir (20 mg/kg) on days 1 and 5 after inoculation. An animal research facility. Thirty-six weanling Hartley guinea pigs. Of the animals who received guinea pig CMV and no cidofovir treatment, 4 of 9 (day 4) and 5 of 9 (days 7 and 28) demonstrated a hearing loss of at least 30 dB. In contrast, none of the animals in the untreated, sham surgery, or cidofovir-treated groups had a hearing loss of greater than 20 dB. This difference was statistically significant for day 4 (P = .04, 1-tailed Fisher exact test), day 7 (P = .01), and day 28 (P = .01). Histologic evaluation of hearing-impaired animals revealed inflammatory infiltrates, particularly in the scala tympani. Fibrosis of the basal turn of the cochlea was observed in 7 of 9 untreated animals and 1 of 9 treated animals. Cidofovir therapy prevents CMV-induced hearing loss and associated histologic changes in guinea pigs.