Official Title: “A Randomized, Double-Blind, Placebo Controlled Crossover Trial Using Valacyclovir to Suppress HSV and HIV Shedding in HIV-1, HSV-2 Coinfected Persons”

The primary objective of this research study is to assess if daily valacyclovir therapy for suppression of HSV-2 reactivation is associated with a decrease in mucosal HIV shedding in individuals co-infected with both HSV-2 and HIV.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Efficacy Study

Study Primary Completion Date: June 2006

Sexually transmitted diseases and genital ulcer disease (GUD) contribute significantly to the spread of HIV, as their presence is associated with higher rates of HIV acquisition in susceptible individuals. Herpes simplex virus-2 (HSV-2) is a major cause of GUD in developed and developing countries.

The primary objective of this research study is to assess if daily valacyclovir therapy for suppression of HSV-2 reactivation is associated with a decrease in mucosal HIV shedding in individuals co-infected with both HSV-2 and HIV.

This study is a randomized, double-blind, placebo-controlled, crossover trial. Sixty men who have sex with men (MSM) will be randomized to first receive either valacyclovir, 1 gram once a day, or matching placebo for 8 weeks. After a 2-week washout period during which all participants receive placebo, subjects then switch to the other treatment for the next 8 weeks.

At screening, informed consent is obtained and individuals will have blood drawn to test antibody status to HIV and HSV and well as to monitor CD4 count and plasma HIV RNA determination. At enrollment, oral, genital, and rectal specimens are obtained and additional blood is drawn. Participants are given a two-week supply of study medication and are instructed on the technique of collecting daily home samples and completing a diary.

Following enrollment, they are asked to collect daily home oral and genital samples, as well as semen samples twice a week, for the full 18 weeks of the study. Participants return to the clinic three times per week for follow-up, for collection of oral and rectal specimens, and additional study medication. Rectal Biopsy is performed at weeks 8 and 18 for those individuals that signed the additional rectal biopsy consent form.

Intervention(s) in this Clinical Trial

• Drug: valacyclovir
  • 1 gram daily for 8 weeks
• Drug: placebo
  • matching placebo for 8 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Placebo Comparator: 2

Primary Measures

• To assess reduction in mucosal HIV shedding associated with daily valacyclovir for suppression of HSV-2 reactivation.
  • Time Frame: 18 weeks
    Safety Issue?: No

Secondary Measures

• To quantify increase in rectal and pharyngeal HIV-1 shedding associated with HSV-1 and HSV-2 reactivation. To determine reduction in systemic HIV RNA during valacyclovir therapy. To evaluate reduction in inflammatory cells and HIV replication.
  • Time Frame: 18 weeks
    Safety Issue?: No

Inclusion Criteria:

• HIV seropositive and HSV-2 seropositive
• MSM (men having sex with men)
• 18 years old or older

Exclusion Criteria:

• Known history of adverse reaction to acyclovir or valacyclovir
• Planned open label use of acyclovir, valacyclovir or famciclovir

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Washington

Overall Clinical Trial Officials and Contacts

Anna Wald, MD, MPH Principal Investigator University of Washington  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00161434

Study ID Number: 02-6505-A

ClinicalTrials.gov Identifier: NCT00161434

Health Authority: United States: Institutional Review Board