a randomized trial to evaluated the suppressive effect of acyclovir on rapidly cleared hsv-2 reactivation

Conditions: Genital Herpes

Summary: 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.

Eligibility 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