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Prevalence of ganciclovir-resistant cytomegalovirus during oral ganciclovir prophylaxis.
Drew WL; Miner RC; Crager M; Stempein MJ; UCSF-MT. Zion Medical
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:164. Unique

A randomized double-blind placebo-controlled study (Syntex 1654) of oral ganciclovir for the prevention of cytomegalovirus (CMV) disease in 725 people infected with HIV showed that ganciclovir was associated with a 49% risk reduction for the development of CMV disease (log rank p less than 0.0001). During oral ganciclovir prophylaxis, cultures of urine (and occasionally blood and/or semen) were performed every 2 months. The last isolate recovered from each patient after at least 90 days of treatment was tested for ganciclovir susceptibility by a plaque reduction assay. Sensitivity was defined as an IC50 less than or equal to 6 micromolar, and resistance was defined as an IC50 greater than 12 micromolar. The average monthly prevalence of positive CMV cultures (90% urine-source) during oral ganciclovir prophylaxis was 11 % compared with 46% for the placebo group. 2 of 39 isolates tested to date from 39 patients receiving ganciclovir for a mean of 251 days (range 112-564) were resistant; 36 isolates were sensitive. All 10 control isolates from patients receiving placebo for a mean of 313 days(range ll2-519)were sensitive. The resistant isolates were obtained from urine cultures after 9 and 10 months of ganciclovir (IC50's=35.8 micromolar and 14.0 micromolar,respectively); after approximately 4 additional months of prophylaxis CMV retinitis was diagnosed in both patients and failed to respond to intravenous ganciclovir. Conclusions: Oral ganciclovir prophylaxis significantly decreased the rate of cytomegalovirus excretion. The prevalence of ganciclovir resistance was low (less than l%) after a mean of 8.3 months of prophylaxis. Resistant virus in two patients was associated with later treatment failure.

Administration, Oral Antiviral Agents/ADMINISTRATION & DOSAGE/*PHARMACOLOGY/ THERAPEUTIC USE Cytomegalovirus/*DRUG EFFECTS Cytomegalovirus Infections/*PREVENTION & CONTROL Double-Blind Method Drug Resistance, Microbial Ganciclovir/ADMINISTRATION & DOSAGE/*PHARMACOLOGY/THERAPEUTIC USE Human Microbial Sensitivity Tests Placebos ABSTRACT