Evaluating Three Grams Daily Valacyclovir in Patients With Chronic Hepatitis C and HSV-2 Infection (Phase I)

Study is a randomized, double-blinded, placebo-controlled, Phase II clinical trial. Participants will be recruited while attending regularly scheduled clinic appointments at the Jackson VA Medical Center. Baseline Visit. Participants will be randomized 1:1 in groups of 10 to receive valacyclovir 1.5 gram orally twice daily or matching placebo. Enrolled participants will complete 12 weeks of assigned therapy.

At the initial visit, participants will complete a short questionnaire detailing past medical/social history and relevant symptoms. Venipuncture will be performed to obtain samples for the laboratory tests. The baseline de-identified serum sample will be obtained from the clinical lab and stored in research-approved freezer space for future confirmation with the Biokit HSV-2 rapid assay. Follow-up visits will be scheduled at two-week intervals after baseline. At each visit, pill-count, compliance and tolerability of medications will be assessed using a short questionnaire. Venipuncture will be performed every four weeks (i.e., at every other follow-up visit) to provide samples for the tests described below. Information from each study visit will be recorded into the chart by the PI or Research Assistant (RA) and entered into an encrypted database on a VA server. Laboratory Tests. HSV-2 infection will be confirmed by performing the Biokit HSV-2 rapid assay on the baseline stored serum sample using methods previously described in this proposal. Laboratory tests will include 1) complete blood count, comprehensive metabolic profile, and quantitative hepatitis C virus (HCV) RNA; and 2) Focus HerpeSelect HSV-1 Immunoglobulin G (IgG) for participants who were seronegative for HSV-1 at baseline. Patient's IL28-B genotype will also be assessed at baseline. The PI will review all laboratory parameters.

Baseline characteristics between the groups will be compared using appropriate parametric tests. Analysis will be intention to treat with the inclusion of all subjects who were randomized to drug or placebo. The primary outcome is change in HCV viral load in the treatment group compared with placebo. Because the investigators are expecting a 0.5 log10 decline in HCV viral load, the investigators will use one-sided parametric tests. All viral loads will be log10-transformed before analysis.

Inclusion criteria

• Documentation of chronic HCV infection with genotype testing and previous positive HerpeSelect HSV-2 IgG assay

Exclusion criteria

• Antiherpes or immunomodulatory therapy during the past 30 days
• HIV or chronic hepatitis B infection
• Decompensated liver disease (ascites, hepatic encephalopathy, coagulopathy, jaundice/icterus)
• Creatinine clearance < 50 ml/min.
• Female subject who is pregnant or nursing
• Gastrointestinal disorder which might result in malabsorption of valacyclovir
• History of erythema multiforme major, thrombotic thrombocytopenia purpura or hemolytic uremic syndrome
• Therapy for hepatitis C in the previous 6 months