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

This study has been completed.
Sponsor:
Collaborators:
GlaxoSmithKline
Asociación Civil Impacta Salud y Educación, Peru
Information provided by:
University of Washington
ClinicalTrials.gov Identifier:
NCT00378976
First received: September 19, 2006
Last updated: August 21, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
HIV Infection
Herpes Simplex
Sexually Transmitted Diseases
Drug: valacyclovir
Drug: matching placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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).

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Reduction in anogenital HIV-1 shedding with suppression of HSV-2 reactivation. [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate HSV-2 suppression with decreased plasma HIV RNA levels [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
  • Assess the effect of daily valacyclovir on pharyngeal shedding in HSV-1 seropositive individuals [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: August 2003
Study Completion Date: July 2004
Arms Assigned Interventions
Experimental: 1 Drug: valacyclovir
500 mg twice-daily oral
Placebo Comparator: 2 Drug: matching placebo
twice daily as per experimental drug

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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 %
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378976

Locations
Peru
Asociacion Civil Impacta Salud y Educacion
Lima, Peru
Sponsors and Collaborators
University of Washington
GlaxoSmithKline
Asociación Civil Impacta Salud y Educación, Peru
Investigators
Principal Investigator: Connie Celum, MD, MPH University of Washington
  More Information

No publications provided by University of Washington

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Connie Celum, MD, MPH, University of Washington
ClinicalTrials.gov Identifier: NCT00378976     History of Changes
Other Study ID Numbers: 21760-A, AI277S7;AI38858;AI30731
Study First Received: September 19, 2006
Last Updated: August 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Washington:
HIV infection
HIV shedding
HSV suppression
Co-infected
MSM
Reactivation
Valacyclovir

Additional relevant MeSH terms:
Infection
HIV Infections
Acquired Immunodeficiency Syndrome
Herpes Simplex
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Herpesviridae Infections
DNA Virus Infections
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Genital Diseases, Male
Genital Diseases, Female
Valacyclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014