Official Title: “A Randomized, Cross-Over Study to Evaluate the Suppressive Effect of Acyclovir on Rapidly Cleared Herpes Simplex Virus Type 2 Genital Reactivation Episodes in Herpes Simplex Virus-2 Seropositive Adults”

We propose to study the episode rate, duration, and quantity of HSV-2 genital shedding in patients taking standard, FDA approved, CDC recommended doses of acyclovir (400 mg PO BID) for HSV-2 suppression compared to taking no medication to better define the effect of acyclovir on short bursts of rapidly cleared HSV-2 shedding. This study will be a randomized, open label, cross-over trial. We hypothesize that short bursts of HSV-2 reactivation will not be suppressed by acyclovir.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Uncontrolled, Crossover Assignment, Efficacy Study

Study Primary Completion Date: September 2011

We propose to study the episode rate, duration, and quantity of HSV-2 genital shedding in patients taking standard, FDA approved, CDC recommended doses of acyclovir (400 mg PO BID) for HSV-2 suppression compared to taking no medication to better define the effect of acyclovir on short bursts of rapidly cleared HSV-2 shedding. This study will be a randomized, open label, cross-over trial.

We propose to perform this study in two study populations. Cohort 1 will be comprised of 25 HSV-2 seropositive, HIV seronegative adults, and Cohort 2 will be comprised of 25 HSV-2 seropositive, HIV seropositive adults with a CD4 count>250 cells/mm3. As suppression of HSV-2 using acyclovir is currently being studied in large, multi-center, international clinical trials as an HIV prevention strategy, these results will have broad implications for public health around the world.

Intervention(s) in this Clinical Trial

• Drug: acyclovir
  • Acyclovir 400 mg PO BID for 28 days

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
• No Intervention: 2

Primary Measures

• Frequency of HSV-2 total shedding from the genital tract as measured by PCR, calculated using a per-day shedding rate in participants treated with suppressive acyclovir as compared to no medication in HIV sero-negative AND HIV seropositive individuals.
  • Time Frame: 9 weeks
    Safety Issue?: No

Secondary Measures

• Frequency of subclinical shedding from the genital tract as measured by PCR, calculated using a per-day shedding rate in participants treated with with suppressive acyclovir as compared to no medication.
  • Time Frame: 9 weeks
    Safety Issue?: No
• Frequency of lesional shedding from the genital tract as measured by PCR, calculated using a per day shedding rate in participants treated with with suppressive acyclovir as compared to no medication.
  • Time Frame: 9 weeks
    Safety Issue?: No
• Number of herpes recurrences, defined clinically as >=1 successive day on which genital lesions are present, in participants treated with with suppressive acyclovir as compared to no medication.
  • Time Frame: 9 weeks
    Safety Issue?: No

Inclusion Criteria:

• COHORT 1: HIV seronegative
• 1. Older than 18 years;
• 2. HSV-2 seropositive by Western Blot;
• 3. not receiving any drugs with known anti-HSV-2 activity for study duration;
• 4. women of child bearing potential who are sexually active with men must be using a medically accepted method of contraception as judged by the investigator;
• 5. women of child-bearing potential must have a negative pregnancy test (urine) at screening visit;
• 6. in general good health, without other serious medical conditions and specifically with normal renal and hepatic function, as determined by the patient's medical history;
• 7. planning to remain resident in the area of the study center for the duration of the study participation;
• 8. HIV seronegative
• COHORT 2: HIV seropositive
• 1. Older than18 years;
• 2. HSV-2 seropositive by Western Blot;
• 3. not receiving any drugs with known anti-HSV-2 activity for study duration;
• 4. women of child bearing potential who are sexually active with men must be using a medically accepted method of contraception as judged by the investigator;
• 5. women of child-bearing potential must have a negative pregnancy test (urine) at screening visit;
• 6. in general good health, without other serious medical conditions and specifically with normal renal and hepatic function, as determined by the patient's medical history;
• 7. planning to remain resident in the area of the study center for the duration of the study participation;
• 8. HIV seropositive
• 9. CD4 count over 250 cell/mm3
• 10. Not taking antiretroviral therapy

Exclusion Criteria:

For both cohorts:

• 1. hypersensitivity to acyclovir or valacyclovir;
• 2. pregnant women;
• 3. Taking immunosuppressive therapies, such as chronic oral steroids or immune modulatory drugs.

For cohort 2:

• 1. CD4 count<250 cell/mm3
• 2. Taking antiretroviral therapy at the time of study entry

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Washington

Overall Clinical Trial Officials and Contacts

Christine Johnston, MD, MPH Principal Investigator University of Washington  

Overall Contact: Christine Johnston, MD, MPH 206-720-4340 cjohnsto@u.washington.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00723229

Study ID Number: 34187-B

ClinicalTrials.gov Identifier: NCT00723229

Health Authority: United States: Institutional Review Board