Effect of Valacyclovir in the Reduction of HSV-2 Recurrence and Shedding

Study Overview
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Brief Summary
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The purpose of the study is to determine how common herpes is among persons with HIV who do not know they have it and if valacyclovir reduces outbreaks of herpes, the amount of HIV in the blood, and the amount of HSV in bodily secretions.

Detailed Description
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Most people with herpes infections do not know they have the infection. HSV infections most often occur in areas in and around the mouth and genital tract. HSV Type 1 (HSV-1) usually causes cold sores or fever blisters and HSV Type 2 (HSV-2) usually causes lesions in the genital or rectal areas. However, HSV-1 can sometimes cause genital herpes and HSV-2 can cause oral lesions (acquired from oral-genital sex). Herpes Simplex is transmitted by contact with someone who is shedding virus in either the mouth or genital tract, usually by kissing or sexual intercourse. While contact with an active sore can cause transmission, so can contact with saliva or genital secretions that are infected, even when the person does not have an obvious sore. This is called asymptomatic shedding of HSV. Once acquired, the virus has the ability to remain inactive in the nervous system in the area of the mouth or genital region. Persons with both HIV and HSV-2 often have shedding of both viruses. We know that persons with HSV-2 tend to have increased amounts of HIV in their blood as well. Recently, research studies have found that taking medicine daily to prevent asymptomatic HSV-2 shedding can reduce the amount of HIV found in the blood and in genital secretions. This study seeks to determine how common herpes is among persons with HIV who do not know they have it and if valacyclovir (FDA approved drug) reduces outbreaks of herpes, the amount of HIV in the blood, and the amount of HSV in bodily secretions.

Official Title
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Seroprevalence of HSV-2 in HIV Infected Subjects and the Effect of Daiy Valacyclovir in the Reduction of HSV-2 Recurrences and Viral Shedding

Conditions
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HIV, HIV Infections

Intervention / Treatment
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* Drug: Valacyclovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 19 years or older HSV-2 (Herpes simplex virus type 2) seropositive as determined by HerpeSelect-2 ELISA Documented HIV-1 seropositive Currently receiving HAART for 3 months or longer CD4 (cluster of differentiation 4) count 350 or greater Women of child bearing potential must agree to use acceptable contraceptive measures during the entire conduct of the study. Acceptable contraceptive methods include one or more of the following: oral hormonal contraceptives, injectable hormonal contraceptives, transdermal hormonal contraceptives, IUD (intrauterine device), diaphragm or cervical cap. Willing and able to provide written informed consent, undergo clinical evaluations, and take study drug as directed Exclusion Criteria: History of symptomatic genital herpes, lesions or symptoms consistent with genital herpes, or recurrent undiagnosed symptoms consistent with genital herpes. Known history of adverse reaction to acyclovir, valacyclovir, or famciclovir. Planned open label use of acyclovir, valacyclovir, ganciclovir, valganciclovir, famciclovir, cidofovir, or foscarnet for oral herpes or other herpes viral infections. Medical history of seizures Renal insufficiency, defined as serum creatinine greater than 1.5 mg/dl AST (aspartate aminotransferase) or ALT (alanine aminotransferase) over 5 times uper limit of normal History of thrombotic microangiopathy For women, pregnancy as confirmed by a urine or serum pregnancy test. Any other condition which, in the opinion of the principal investigator, may compromise the subject's ability to follow study procedures and complete the study. Participants with active bacterial STDs (sexually transmitted diseases) may be treated and be eligible for enrollment 14 days after STD therapy is discontinued and symptoms have resolved.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Valacyclovir<br>This is the arm taking Valacyclovir | Drug: Valacyclovir<br>* 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks<br>* Other names: There are no other names;|
| Placebo Comparator: Placebo<br>This is the arm taking the placebo | Drug: Placebo<br>* Dosage: Two tablets once a day for 24 weeks<br>* Other names: There are no other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Herpes Simplex Virus Type 2 Recurrence | Number of recurrences of genital herpes | 24 Weeks | 
| CD4 Count | CD4 count as measured after 24 weeks of placebo versus valacyclovir. Reports as cells/ml | 24 weeks | 
| Number of Participants With an HIV Viral Load of <500 Copies/ml | Number of participants with an HIV Viral Load of <500 copies/ml at 24 weeks | 24 weeks | 
| Rate of Asymptomatic HSV-2 Genital Shedding | Proportion of days on which HSV shedding was observed. This part of the study was performed in a subset of participants (N = 34). Participant collected daily genital specimens for 8 weeks starting at week 16 and continuing through week 24 of the study. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HSV-2, Herpes Simplex, HSV Type 2, HIV/HSV, treatment experienced