Please select the eligibility criteria that correspond to the clinical trial below.
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
Brief 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.


Options:
A: Inclusion Criteria:

1. 18 years or older;
2. HSV-2 seropositive by Western Blot;
3. not receiving any drugs with known anti-HSV-2 activity for study duration;
4. history of primary genital herpes infection within past 6 months OR history of 4 or more HSV recurrences per year during the past year OR 4 or more recurrences per year prior to initiation of suppressive antiviral therapy;
5. able to comply with the study protocol;
6. 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;
7. women of child-bearing potential must have a negative pregnancy test (urine) at screening visit;
8. 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;
9. planning to remain resident in the area of the study center for the duration of the study participation;
10. HIV seronegative.

Exclusion Criteria:

1. hypersensitivity to acyclovir or valacyclovir;
2. pregnant women;
3. HIV positive or other immunosuppressed state, including chronic steroid use. Intermittent nasal or topical steroids are acceptable
B: Inclusion Criteria:

* 18 years or older;
* HSV-2 seropositive by Western Blot;
* not receiving any drugs with known anti-HSV-2 activity for study duration;
* history of primary genital herpes infection within past 6 months OR history of 4 or more HSV recurrences per year during the past year OR 4 or more recurrences per year prior to initiation of suppressive antiviral therapy; or shedding HSV-2 from genital mucosa on \>25% of days in shedding session performed at the VRC within the last 2 years.
* able to comply with the study protocol;
* 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.

Exclusion Criteria:

* hypersensitivity to acyclovir or valacyclovir;
* pregnant women;
* HIV positive or other immunosuppressed state, including chronic steroid use. Intermittent nasal or topical steroids are acceptable
C: Inclusion Criteria:

* At least 18 years old
* History of at least 4 recurrences of genital herpes in the preceding 12 months
* Lesions located on the external genitalia or anogenital region
* Willing to discontinue suppressive treatment
* Documented positive herpes simplex virus (HSV)
* General good health, and history of normal renal function

Exclusion Criteria:

* Women of childbearing potential not using approved form of contraceptive
* Pregnant or nursing women
* History of hypersensitivity to famciclovir, valacyclovir, or acyclovir
* Known to be immunosuppressed
* Known to have renal dysfunction
* Receiving anti-herpes therapy
* Known to have other genital tract disorders
* Known to have condition which could interfere with drug absorption

Additional protocol-defined inclusion/exclusion criteria may apply.
D: 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

Answer: D