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

Condition(s) targeted: Genital Herpes

Intervention: acyclovir (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: University of Washington

Official(s) and/or principal investigator(s):
Christine Johnston, MD, MPH, Principal Investigator, Affiliation: University of Washington

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

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.

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

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

Primary outcome: 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.

Secondary outcome:

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.

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.

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.

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

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

University of Washington Virology Research Clinic, Seattle, Washington 98122, United States; Recruiting
Christine Johnston, MD, MPH, Phone: 206-720-4340, Email: cjohnsto@u.washington.edu
Christine Johnston, MD, MPH, Principal Investigator

Starting date: August 2008
Ending date: September 2011
Last updated: August 31, 2009