Valganciclovir for Suppression of Human Herpesvirus–8 Replication: A Randomized, Double‐Blind, Placebo‐Controlled, Crossover Trial
Departments of 1Medicine, 2Laboratory Medicine, and 3Epidemiology, University of Washington and the 4Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington
Background.
Human herpesvirus–8 (HHV‐8) replication is critical in the induction and maintenance of Kaposi sarcoma, primary effusion lymphoma, and some cases of Castleman disease. In vitro and observational studies suggest that ganciclovir inhibits HHV‐8 replication, but no randomized clinical trials have been conducted.
Methods.A total of 26 men infected with HHV‐8 were randomized to receive 8 weeks of valganciclovir administered orally (900 mg once per day) or 8 weeks of placebo administered orally. After a 2‐week washout period, participants in each group received the study drug they had not yet taken (either valganciclovir or placebo), for 8 additional weeks. Oral swab samples were collected daily during the study, and HHV‐8 and CMV DNA were quantified by real‐time PCR.
Results.A total of 16 human immunodeficiency virus (HIV)–positive men and 10 HIV‐negative men enrolled in and completed the study. Of the 3439 swab samples that participants had been expected to provide, 3029 (88%) were available for analysis. HHV‐8 was detected on 44% of swabs collected from participants who were receiving placebo, compared with 23% of swabs collected from participants who were receiving valganciclovir (relative risk [RR], 0.54 [95% confidence interval {CI}, 0.33–0.90]; 
). Valganciclovir reduced oropharyngeal shedding of cytomegalovirus by 80% (RR, 0.20 [95% CI, 0.08–0.48]; 
). Shedding of HHV‐8 and shedding of cytomegalovirus were independent. Hematologic, renal, or hepatic toxicities were no more common among participants who received the active drug, compared with those who received placebo, though participants who received valganciclovir reported more days of diarrhea.
Conclusions.Valganciclovir administered orally once per day is well tolerated and significantly reduces the frequency and quantity of HHV‐8 replication.
Received 24 December 2007; accepted 28 December 2007; electronically published 20 May 2008.
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(See the editorial commentary by Crumpacker, on pages 6–7.)
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Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grants K23 AI‐054162 to C.C., K24 AI‐071113 to A.W., P01 AI‐30731 to A.W. and L.C., and U19 AI‐31448 to A.W. and L.C.); Roche Laboratories (Investigator‐Initiated Research Grant to A.W. and donation of study drug and placebo); Doris Duke Charitable Foundation (Clinical Scientist Development Award to C.C.).