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HSV-2 Suppression to Reduce HIV-1 Levels in HIV-1, HSV-2 Co-infected Men.

Primary Purpose

HIV Infection, Herpes Simplex, Sexually Transmitted Diseases

Status
Completed
Phase
Phase 3
Locations
Peru
Study Type
Interventional
Intervention
valacyclovir
matching placebo
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infection focused on measuring HIV infection, HIV shedding, HSV suppression, Co-infected, MSM, Reactivation, Valacyclovir

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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 %

Sites / Locations

  • Asociacion Civil Impacta Salud y Educacion

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

Reduction in anogenital HIV-1 shedding with suppression of HSV-2 reactivation.

Secondary Outcome Measures

Evaluate HSV-2 suppression with decreased plasma HIV RNA levels
Assess the effect of daily valacyclovir on pharyngeal shedding in HSV-1 seropositive individuals
Determine the temporal pattern of HIV shedding in the rectum, pharynx and semen with respect to mucosal HSV-1 and HSV-2 reactivation; Determine HSV-2 suppression and HIV replication within rectal mucosa.

Full Information

First Posted
September 19, 2006
Last Updated
August 21, 2013
Sponsor
University of Washington
Collaborators
GlaxoSmithKline, Asociación Civil Impacta Salud y Educación, Peru
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1. Study Identification

Unique Protocol Identification Number
NCT00378976
Brief Title
HSV-2 Suppression to Reduce HIV-1 Levels in HIV-1, HSV-2 Co-infected Men.
Official 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).
Study Type
Interventional

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
August 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Washington
Collaborators
GlaxoSmithKline, Asociación Civil Impacta Salud y Educación, Peru

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Herpes simplex virus type 2 (HSV-2) is common among HIV infected persons. HSV-2 reactivation is associated with increased plasma and genital HIV-1 levels, and in vitro, HSV-2 upregulates HIV transcription. The trial assessed whether HSV-2 suppression reduces rectal and plasma HIV-1 levels in HIV-1, HSV-2 co-infected men who have sex with men (MSM). Conducted in Lima Peru, 20 antiretroviral naive HIV-1 and HSV-2 seropositive MSM with CD4 >200 were randomly assigned to receive valacyclovir 500 mg bid or placebo for 8 weeks, than a 2 week washout period, followed by the alternative regimen for 8 weeks. Men collected daily home anogenital swabs for HSV DNA PCR, had three weekly anoscopy procedures for collection of rectal mucosal secretions for HIV-1 RNA, HSV DNA, and weekly plasma HIV-1 RNA by PCR. Outcomes were plasma and rectal HIV-1 levels by study arm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection, Herpes Simplex, Sexually Transmitted Diseases
Keywords
HIV infection, HIV shedding, HSV suppression, Co-infected, MSM, Reactivation, Valacyclovir

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
valacyclovir
Intervention Description
500 mg twice-daily oral
Intervention Type
Drug
Intervention Name(s)
matching placebo
Intervention Description
twice daily as per experimental drug
Primary Outcome Measure Information:
Title
Reduction in anogenital HIV-1 shedding with suppression of HSV-2 reactivation.
Time Frame
18 weeks
Secondary Outcome Measure Information:
Title
Evaluate HSV-2 suppression with decreased plasma HIV RNA levels
Time Frame
18 weeks
Title
Assess the effect of daily valacyclovir on pharyngeal shedding in HSV-1 seropositive individuals
Time Frame
18 weeks
Title
Determine the temporal pattern of HIV shedding in the rectum, pharynx and semen with respect to mucosal HSV-1 and HSV-2 reactivation; Determine HSV-2 suppression and HIV replication within rectal mucosa.
Time Frame
18 weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 %
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Connie Celum, MD, MPH
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asociacion Civil Impacta Salud y Educacion
City
Lima
Country
Peru

12. IPD Sharing Statement

Citations:
PubMed Identifier
19169140
Citation
Zuckerman RA, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Magaret A, Wald A, Corey L, Celum C. HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men. AIDS. 2009 Feb 20;23(4):479-83. doi: 10.1097/QAD.0b013e328326ca62.
Results Reference
derived
PubMed Identifier
18008230
Citation
Zuckerman RA, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Zuniga R, Magaret AS, Wald A, Corey L, Celum C. Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial. J Infect Dis. 2007 Nov 15;196(10):1500-8. doi: 10.1086/522523. Epub 2007 Oct 31.
Results Reference
derived

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HSV-2 Suppression to Reduce HIV-1 Levels in HIV-1, HSV-2 Co-infected Men.

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