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Prevalence of ganciclovir-resistant cytomegalovirus during oral ganciclovir prophylaxis.


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


Information in this article was accurate in November 30, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.