The purpose of the study is to use valganciclovir to define the role of antiviral therapy in suppression of HHV-8 shedding in HHV-8 seropositive men. Our hypothesis is that valganciclovir will substantially reduce the frequency of detection and amount of HHV-8 in the mouth.

The purpose of the study is to use valganciclovir to define the role of antiviral therapy in suppression of HHV-8 shedding in HHV-8 seropositive men. Our hypothesis is that valganciclovir will substantially reduce the frequency of detection and amount of HHV-8 in the mouth. Such reduction will serve to confirm that the mouth is the site of active HHV-8 replication. If valganciclovir is found to be effective, the findings from this proposal would serve as the basis for a clinical trial with valganciclovir for prevention of Kaposi's Sarcoma (KS) in high-risk HHV-8 seropositive persons.

After informed consent, all subjects will undergo medical history, physical examination and screening laboratory examination. Eligible patients will return to clinic for randomization to receiver either valganciclovir 900 mg qd or placebo. Participants will receive a diary for noting adverse events and concurrent medications. The clinician will instruct the participants on collection of mouth swabs and provide Dacron swabs, vials with PCR media and pre-printed labels. Subjects will be asked to obtain a swab of oral mucosa every morning. Clinic visits every other week will serve to review interim medical history and diaries for adverse events, collect PCR swabs, dispense additional medication and draw safety labs. The study uses a double-blind, randomized placebo design. Therefore, participants will not know whether they will be taking a placebo or active medication at any time during the study. Due to the crossover study design, however, all participants will receive the same amount of placebo and study drug over the duration.

Inclusion Criteria:

• 18 years or older
• HHV-8 seropositive or previous evidence of HHV-8 shedding
• a frequent shedder of HHV-8
• not receiving any drugs with known anti-HHV-8 activity for study duration
• able to comply with the study protocol
• agree to HIV testing

Exclusion Criteria:

• history of evidence of CMV disease
• hypersensitivity to ganciclovir or valganciclovir
• use of high-dose acyclovir, valacyclovir, famciclovir, ganciclovir, foscarnet, or cidofovir
• neutropenia
• renal insufficiency with serum creatinine greater than 1.5mg.ml or CrCl less than 60
• AST or ALT greater than 5 times upper limit of normal
• concurrent administration of medications which are often associated with severe neutropenia or thrombocytopenia
• concurrent administration of probenecid or didanosine