Defining the optimal treatment regimens for HHV-8 infection, including the treatment of KS and multicentric Castleman's disease

Corey Casper, MD, MPH, Anna Wald, MD, MPH, and Lawrence Corey, MD

1) The Efficacy of Antiviral Therapy in the Reduction of HHV-8 Oropharyngeal Shedding

A study is currently underway using 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.   Shedding of latent or defective virus would not be affected by valganciclovir, as this class of drugs requires viral replication for activity.   If valganciclovir were found effective, the findings from this proposal would serve as the basis for a clinical trial with valganciclovir for prevention of KS in high-risk HHV-8 seropositive persons. The aims of this study are: to evaluate the effect of oral daily valganciclovir on HHV-8 shedding from the mouth in HIV-seronegative and HIV-seropositive MSM, and to determine the safety of oral daily valganciclovir in HIV-seronegative and HIV seropositive MSM.

To measure the effect of oral valganciclovir on shedding of HHV-8, we are conducting a double-blind, randomized, placebo-controlled cross-over study of 32 HHV-8 seropositive MSM who have demonstrated in previous studies to be frequent oral shedders of HHV-8, defined as detection of HHV-8 on at least 40% of days sampled.   Men who are seropositive for HHV-8 will be randomized 1:1 to receive either valganciclovir 900 mg qd or placebo.   The randomization will be stratified by HIV status, with 16 participants (8 HIV seropositive and 8 HIV seronegative) in each arm. After 8 weeks on the initial treatment, each participant will be crossed over to a second treatment arm for 8 weeks.   The treatment periods will be separated by a 2-week washout period of placebo.

2) Ganciclovir for the Treatment of Multicentric Castleman's Disease

This descriptive will evaluate the clinical and virologic response of Human Immunodeficiency Virus (HIV) and Human Herpesvirus 8 (HHV-8)-associated Multicentric Castleman's disease (MCD) to ganciclovir. Patients meeting diagnostic criteria for MCD will be prospectively enrolled. Assessments of HHV-8 viremia, IL-6 and CRP levels will be made at study entry, termination and with each symptomatic flare of MCD. Weekly oral swabs will be collected for quantitative HHV-8 DNA PCR. During symptomatic flares of MCD, a detailed clinical assessment will be obtained, along with daily quantitative HHV-8 PCR from PBMC and saliva. Treatment with oral valganciclovir or intravenous ganciclovir will be initiated. Analysis of the data will attempt to determine the response of MCD to preparations of ganciclovir, and whether either therapy or response correlate to HHV-8 viremia, IL-6 or CRP levels.