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

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.

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