A Randomized Trial to Evaluated the Suppressive Effect of Acyclovir on Rapidly Cleared HSV-2 Reactivation

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.

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 Investigator: University of Washington Other

Overall Clinical Trial Officials and Contacts

Christine Johnston, MD, MPH Principal Investigator University of Washington  

Information obtained from ClinicalTrials.gov on February 12, 2012

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