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

• 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]

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.

• Active Comparator: 1
  Intervention: Drug: acyclovir
• No Intervention: 2

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