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:

* Males presenting at the primary health care clinic with a genital ulcer
* Age 18 years or older
* Willing and able to give informed consent
* Willing to be tested for HSV and HIV
* Willing and able to comply with the study protocol including follow-up visits
* Willing to accept therapy by chance

Exclusion Criteria:

* Extensive ulceration
* Ulceration \>1 month
* History of adverse reaction to acyclovir
* Taking suppressive therapy for genital herpes
* History of renal insufficiency or proteinuria
B: Inclusion Criteria:

* Clinically confirmed ulcer
* Resident of city or planning to stay for 1 month
* Be a women

Exclusion Criteria:

* Pregnant women
* Menstruating women
* Positive protein urine test
C: 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
D: Inclusion Criteria:

* HIV uninfected
* Willing to receive HIV results
* Willing to be circumcised
* Parent or guardian willing to provide informed consent if applicable
* Hemoglobin of 8 grams/dl or less
* Intend to stay in Rakai, Uganda, for at least 1 year and are available for follow-up for 1 year

Exclusion Criteria:

* Already circumcised or partially circumcised
* Anatomical abnormality of the penis (e.g., hypospadias, severe phimosis) that may put the participant at risk if circumcised
* Medical conditions that require therapeutic circumcision
* Medical condition that contraindicates surgery or use of local anesthesia

Answer: C