Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized,Double-Blind , Placebo-Controlled Crossover Trial of Antivirals for Suppression of HSV and HIV Shedding in HIV-1, HSV-2 Co-infected Persons
Brief Summary: Over 80% of HIV-1 infected persons are also seropositive for HSV-2. Increasingly, clinical and epidemiologic evidence show the role of HSV in increasing HIV infectiousness. The evidence suggests that HSV is an important co-factor in HIV transmission.

The trial's purpose is to assess the reduction in HIV systemic and mucosal replication associated with valacyclovir for suppression of HSV-2 reactivation.

This randomized, double-blind, placebo controlled crossover trial of 20 HIV/HSV-2 co-infected women assessed the effects of daily valacyclovir on HIV-1 levels in blood and body fluids.


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:

* Infection with HIV-1 and HSV-2
* If required to take antiretrovirals according to WHO recommendations, should be on HAART for at least 4 months
* Written informed consent

Exclusion Criteria:

* Pregnancy or willing to be pregnant during the next 6 months
* Breastfeeding
* Renal failure
* Expected non-compliance with follow-up or study treatment
C: Inclusion Criteria:

Potential index (HIV-infected) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study:

* Of legal age to provide independent informed consent for research per local regulations and guidelines.
* Able and willing to provide written informed consent to be screened for and to take part in the study. (Note: Index participants who are not willing to provide genital tract specimens for HIV viral load quantitation, but are willing to undergo all other study procedures, will be considered eligible for inclusion in the study.)
* Part of a heterosexual couple in which one partner meets the study eligibility criteria for index participants and the other partner meets the study eligibility criteria for partner participants. Couples are defined as partners who are sexually active and plan to remain in the relationship for at least one year. Each site will develop appropriate criteria for determining whether a couple is likely to remain in the relationship (i.e., married, duration of partnership, cohabitation, have children).
* Has had vaginal intercourse with the partner participant at least three times in the last three months.
* Plans to maintain his/her relationship with the partner participant for the next 24 months.
* HIV-infected based on positive EIA.
* HSV-2-seropositive based on the Focus HSV-2 EIA (performed by study staff) with an index ratio of at least 3.5 or if Focus EIA IN 1.1-3.4, confirmed by HSV-2 WB dot-blot performed at the UW.
* CD4 cell count (performed by study staff) of at least 250 cells/mm3.
* No history of any clinical AIDS-defining diagnoses.
* Able and willing to provide adequate locator information for study retention purposes, as defined by local standard operating procedures.

Potential partner (HIV-uninfected at enrollment) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study:

* Of legal age to provide independent informed consent for research per local regulations and guidelines.
* Able and willing to provide written informed consent to be screened for and to take part in the study.
* Part of a heterosexual couple in which one partner meets the study eligibility criteria for index participants and the other partner meets the study eligibility criteria for partner participants.
* Has had vaginal intercourse with the study partner at least three times in the last three months.
* Plans to maintain his/her relationship with the index participant for the next 24 months.
* HIV-uninfected based on negative HIV EIA tests.
* Able and willing to provide adequate locator information for study retention purposes, as defined by local standard operating procedures.

Exclusion Criteria:

Potential index (HIV-infected) participants who meet any of the following criteria (by self-report, unless otherwise indicated) will be excluded from the study:

* Current use of combination antiretroviral therapy
* Known history of adverse reaction to acyclovir.
* Known history of persistent genital ulcers unresponsive to episodic acyclovir therapy.
* Known plans to re-locate or travel away from the study site for more than two consecutive months during the next 24 months.
* Pregnant, based on participant self-report or urine testing performed by study staff. (Note: Self-reported pregnancy is adequate for exclusion from the study. A documented negative test performed by study staff is required for inclusion.)

Potential partner participants who meet any of the following criteria (by self-report, unless otherwise indicated) will be excluded from the study:

* Has had sexual intercourse with a partner other than the index participant in the last two months.
* Known plans to re-locate or travel away from the study site for more than two consecutive months during the next 24 months.
D: Inclusion Criteria:

* Greater than 18 years old woman,
* Documented HIV-1 seropositive,
* CD4 count greater than 200,
* Not on HIV antiretroviral therapy,
* HSV-2 seropositive as determined by Focus EIA (IN \>3.5)
* Not intending to move out of the area for the duration of study participation.
* Willing and able to:provide independent written informed consent;undergo clinical evaluations;take study drug as directed;adhere to follow-up schedule.
* Bacterial STDs (symptomatic STD syndromes or laboratory-confirmed asymptomatic gonorrhea and syphilis) are treated within two weeks of study enrollment and random assignment.

Exclusion Criteria:

Women who meet any of the following criteria are not eligible for this study:

* Known history of adverse reaction to valacyclovir, acyclovir or famciclovir;
* Planned open label use of acyclovir, valacyclovir, or famciclovir
* Known medical history of seizures
* Known renal failure, serum creatinine \>2.0mg/dl
* Hematocrit \< 30 %

Answer: D