Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind, Placebo-controlled Crossover Trial of Valacyclovir for Suppression of HSV and HIV Shedding in HIV-1, HSV-2 Coinfected Men Who Have Sex With Men (MSM).
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 that HSV is an important cofactor in HIV transmission.

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

This proof-of-concept, randomized, double-blind, placebo controlled crossover trial of 20 HIV/HSV-2 co-infected men, assessed the effects of daily valacyclovir on HIV-1 levels in the plasma and rectal mucosa secretions.


Options:
A: Inclusion Criteria:

* The subject is 18 to 55 years of age.
* The subject has signed written informed consent.
* The subject has untreated primary \[darkfield or Treponema (T.) pallidum by a rapid, direct, fluorescent antibody darkfield (DFA-TP)\] positive genital ulcers, secondary (based on classical palmar/plantar rash, condylomata lata, mucous patches, etc. or darkfield or DFA-TP positive lesions), or early latent syphilis (e.g., current reactive serologic tests for syphilis (STS), and a documented non-reactive STS or documented sexual exposure to a known early latent, primary or secondary syphilis patient in last 12 months; identification of this sexual contact must occur within 60 days of admission into the study).
* The subject has laboratory evidence of syphilis, i.e., reactive serologic test for syphilis (RPR).
* The subject is not pregnant, as documented by a negative urine or serum pregnancy test, or lactating.
* The subject is willing to have an HIV test, and, participate in HIV counseling and return to the clinic for follow-up treatment.

Exclusion Criteria:

* The subject does not have reactive serologic tests for syphilis.
* The subject has latent syphilis of unknown duration, late latent syphilis or evidence of neurosyphilis.
* The subject has a known or suspected allergy to macrolide or azalide antibiotics.
* The subject has a known or suspected sexually transmitted disease (STD), other than syphilis requiring treatment with a drug, other than azithromycin, active against T. pallidum.
* The subject has used antibiotics active against T. pallidum in the preceding 30 days. (Note: the use of antimicrobials known to NOT be effective against T. pallidum such as quinolones, sulfonamides, trimethoprim, metronidazole and spectinomycin will be allowed).
* The subject is known to be HIV positive prior to enrollment.
* The subject has suspected or known ongoing drug use that might interfere with study participation and follow-up treatment.
* The subject has a history of cardiovascular disease, known immunosuppression, or known AIDS, which might compromise response to therapy.
* The subject is judged by the investigators to be unlikely to reliably participate in the study follow-up.
* The subject has used any investigational drugs in the past 30 days.
* The subject has any other condition that may impair drug absorption (malabsorption syndrome or active peptic ulcer disease).
B: Inclusion Criteria For All Participants:

* HIV-uninfected
* HSV-2 infected
* Plans to stay in the area for the duration of study participation
* Willing and able to provide consent, undergo clinical evaluations, take study drugs, adhere to follow-up schedule, and provide adequate locator information

Inclusion Criteria for MSM:

* At least 1 episode of anal intercourse with another man within 6 months of study entry

Inclusion Criteria for WSM:

* At least 1 episode of unprotected vaginal sex within 6 months of study entry

Exclusion Criteria For All Participants:

* Current enrollment in another HIV vaccine or prevention trial
* History of adverse reaction to acyclovir
* Current or planned use of famiciclovir, valacyclovir, or acyclovir for genital HSV. Use of short-course antiviral therapy for herpes zoster after enrollment is allowed.
* Known plans for travel away from study site for more than 2 months

Exclusion Criteria for MSM:

* In a mutually monogamous relationship with an HIV uninfected partner throughout the past 2 years
* Reported sex at birth as female

Exclusion Criteria for WSM:

* Pregnancy at screening or enrollment
C: 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 %
D: Inclusion Criteria:

* Greater than 18 years old,
* 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:

MSM 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