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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Genital Herpes

Intervention / Treatment
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* Drug: acyclovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COHORT 1: HIV seronegative Older than 18 years; HSV-2 seropositive by Western Blot; not receiving any drugs with known anti-HSV-2 activity for study duration; 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; women of child-bearing potential must have a negative pregnancy test (urine) at screening visit; 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; planning to remain resident in the area of the study center for the duration of the study participation; HIV seronegative COHORT 2: HIV seropositive Older than18 years; HSV-2 seropositive by Western Blot; not receiving any drugs with known anti-HSV-2 activity for study duration; 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; women of child-bearing potential must have a negative pregnancy test (urine) at screening visit; 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; planning to remain resident in the area of the study center for the duration of the study participation; HIV seropositive CD4 count over 250 cell/mm3 Not taking antiretroviral therapy Exclusion Criteria: For both cohorts: hypersensitivity to acyclovir or valacyclovir; pregnant women; Taking immunosuppressive therapies, such as chronic oral steroids or immune modulatory drugs. For cohort 2: CD4 count<250 cell/mm3 Taking antiretroviral therapy at the time of study entry

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: acyclovir<br>* Acyclovir 400 mg PO BID for 28 days<br>|
| No Intervention: 2<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Seronegative and HIV Seropositive Individuals. |  | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantity of HSV Detected, Median | Median quantity of HSV detected, among swabs with any HSV detected | 9 weeks | 
| Number of Genital HSV Shedding Episodes | The number of HSV shedding episodes. A shedding episode is defined as any number of positive swabs preceded and followed by 2 negative swabs | 9 weeks | 
| Duration of Genital HSV Shedding Episodes | Median duration of HSV shedding episodes, in hours | 9 weeks |