Susceptibility of human cytomegalovirus to cidofovir is unchanged after limited in vivo exposure to various regimens of drug

Abstract

Cidofovir [1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine] susceptibility among 29 paired pre- and post-cidofovir exposure isolates from 22 patients enrolled in phase I/II clinical trial, GS-92-101, was determined. This trial was designed to evaluate the safety and antiviral effects of cidofovir in patients with AIDS and asymptomatic shedding of human cytomegalovirus (HCMV) in semen with no evidence of end-organ HCMV disease and no prior anti-HCMV therapy. These patients received a median cumulative dose of 30 mg/kg (range, 3-67) administered over a median of 8 weeks (range, 2-38). The IC50 values of preexposure isolates ranged from <0.5 to 1.85 and for postexposure isolates from <0.5 to 2 uM. Thus, no significant changes in cidofovir susceptibilities have been noted for HCMV during the various regimens of cidofovir administrated in this clinical trial.