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

• Effect of HSV-2 suppression on HCV viral load. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  Measure the decline in serum HCV viral load in patients who have chronic hepatitis C and HSV-2 infection who receive the 3 grams daily valacyclovir versus placebo for 12 weeks.
  
  

• Effect of 3 grams daily valacyclovir on liver tests in hepatitis C infection [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
  The investigators will assess the number of patients with chronic hepatitis C and HSV-2 co-infection who experience symptomatic and asymptomatic elevation liver function tests to valacyclovir 3 grams daily for 12 weeks.
  
  

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 VAMC. 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 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 HCV RNA; and 2) Focus HerpeSelect HSV-1 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 we are expecting a 0.5 log10 decline in HCV viral load, we will use one-sided parametric tests. All viral loads will be log10-transformed before analysis. We anticipate using a higher cut-off will eliminate false positive HerpeSelect HSV-2 IgG assays.