Trial record 17 of 26 for:    " August 15, 2007":" September 14, 2007"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Trial to Study the Effect of Dose of Herpes Simplex Virus-2 (HSV-2) Suppressive Therapy on HSV and HIV

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Jared Baeten, University of Washington
ClinicalTrials.gov Identifier:
NCT00527618
First received: September 7, 2007
Last updated: January 18, 2013
Last verified: January 2013
  Purpose

To compare the effect of high-dose valacyclovir (1 gram orally twice daily) versus standard-dose acyclovir (400 mg orally twice daily) on the frequency of genital HSV reactivation and on plasma HIV-1 levels among HSV-2/HIV-1 co-infected individuals. The investigators hypothesize that high-dose valacyclovir will result in greater reduction in plasma HIV-1 and genital HSV reactivation.


Condition Intervention Phase
Genital Herpes
HIV Infection
Drug: valacyclovir
Drug: acyclovir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Crossover Trial of the Effect of Dosing of Daily HSV-2 Suppressive Therapy on HSV Reactivation and Plasma HIV-1 Levels Among HIV-1/ HSV-2 Co-infected Persons

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • The Quantity of HIV-1 RNA in Plasma While on 400 mg Twice Daily of Acyclovir Versus 1000 mg Twice Daily of Valacyclovir. [ Time Frame: 26 weeks (12 weeks per drug intervention) ] [ Designated as safety issue: No ]
    Weekly measurements of plasma HIV-1 RNA on each drug were compared. The primary analysis was of the average difference in plasma HIV-1 RNA on valacyclovir and acyclovir as determined by a linear mixed model. The median of the average per-participant plasma HIV-1 RNA levels on valacyclovir and valacyclovir is also listed.

  • The Genital HSV Shedding Rate While on 400 mg Twice Daily of Acyclovir Versus 1000 mg Twice Daily of Valacyclovir. [ Time Frame: The first four weeks of each intervention ] [ Designated as safety issue: No ]
    HSV DNA quantitated from daily self-collected genital swabs for the first four weeks of each drug intervention. The shedding rate was determined by the combined number of swabs with HSV detected divided by the combined number of swabs collected from participants, multiplied by 100.


Secondary Outcome Measures:
  • The Effect of Valacyclovir 1 Gram Twice Daily Compared to Acyclovir 400 mg Twice Daily on the Percentage of Days With Genital Herpes Lesions. [ Time Frame: 26 weeks (12 weeks per drug intervention) ] [ Designated as safety issue: No ]
    The percentage of days with genital herpes lesions was determined by the combined diary days in which genital lesions were recorded divided by the combined number of diary days for participants in the first four weeks of each drug intervention, multiplied by 100.

  • The Effect of Valacyclovir 1 g Twice Daily Compared With Acyclovir 400 mg Twice Daily on the Quantity of Genital HSV Detected During Shedding Episodes. [ Time Frame: The first four weeks of each intervention ] [ Designated as safety issue: No ]
    HSV DNA was quantitated from daily self-collected genital swabs for the four weeks of each drug intervention. The quantity of genital HSV DNA present, when HSV DNA was detected, was compared.

  • The Safety of Valacyclovir 1 Gram Orally Twice Daily in HIV-1 Seropositive Persons. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Sub-Study: To Evaluate the Kinetics of Plasma HIV-1 Decline Over the First Three Days of High-dose Valacyclovir Administration. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Plasma HIV-1 RNA was measured one day prior to, at initiation, and at 6, 24, 48, and 72 hours after initiating valacyclovir. Measurements at 24, 48, and 72 hours were used to determine the rate of HIV-1 RNA decline.


Enrollment: 28
Study Start Date: December 2007
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard-dose acyclovir
acyclovir 400 mg orally twice daily for 12 weeks.
Drug: acyclovir
acyclovir 400 mg orally twice daily for 12 weeks.
Other Name: Zovirax
Experimental: High-dose valacyclovir
valacyclovir 1000 mg orally twice daily for 12 weeks.
Drug: valacyclovir
valacyclovir 1000 mg orally twice daily for 12 weeks.
Other Name: Valtrex

Detailed Description:

We propose to conduct a randomized, open-label, cross-over study of 38 individuals who are HIV-1 seropositive and HSV-2 seropositive. Both men and women will be recruited for the study. Participants must not be on antiretroviral therapy and must not be planning to initiate antiretroviral therapy during the anticipated study period. Participants will be randomized 1:1 to receive acyclovir 400 mg twice daily or valacyclovir 1000 mg twice daily. After 12 weeks on the initial treatment, each participant will be crossed over to the alternative treatment arm for 12 weeks. The treatment periods will be separated by a 2-week washout period. During the first four weeks of each treatment period (i.e. weeks 1-4 and weeks 15-18), participants will provide self-collected genital swabs daily for HSV DNA quantification. Each week during the entire study period plasma samples will be collected from participants for HIV-1 RNA quantification.

Open-label acyclovir and valacyclovir will be used for this trial, as the primary outcome measures (genital HSV and plasma HIV-1) are unlikely to be influenced by knowledge of treatment assignment. However, laboratory staff performing plasma HIV-1 and genital HSV measurements will not be aware of treatment assignment.

Optional Sub-Study A: Sub-study A will be offered to study participants. The purpose of sub-study A is to measure the effect of valacyclovir twice daily on plasma HIV-1 replication.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Documented HIV-1 seropositive
  • Not on HIV-1 antiretroviral therapy nor planning to initiate antiretroviral therapy during the study period
  • Detectable HIV-1 plasma viral load
  • HSV-2 seropositive as determined by western blot
  • Not intending to move out of the area for the duration of study participation
  • Willing and able to provide independent written informed consent
  • Willing and able to undergo clinical evaluations
  • Willing and able to take study drug as directed
  • Willing and able to adhere to follow-up schedule

Exclusion Criteria:

  • Known history of adverse reaction to acyclovir, valacyclovir, or famciclovir
  • Planned open label use of acyclovir, valacyclovir, or famciclovir
  • History of evidence of CMV disease
  • Known medical history of seizures
  • Known renal insufficiency, defined as serum creatinine greater than 1.5 mg/dl
  • AST or ALT greater than 3 times upper limit of normal
  • Hematocrit less than 30 %
  • Neutropenia, defined as absolute neutrophil count less than 1000
  • Thrombocytopenia, defined as platelet count less than 75,000
  • History of thrombotic microangiopathy
  • For women, pregnancy as confirmed by a urine pregnancy test
  • Any other condition which, in the opinion of the principal investigator, may compromise the ability to follow study procedures and complete the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00527618

Locations
United States, Washington
University of Washington Virology Research Clinic
Seattle, Washington, United States, 98122
Sponsors and Collaborators
University of Washington
GlaxoSmithKline
Investigators
Principal Investigator: Jared Baeten, MD, PhD University of Washington
Study Director: Anna Wald, MD, MPH University of Washington
  More Information

No publications provided

Responsible Party: Jared Baeten, Principal Investigator, University of Washington
ClinicalTrials.gov Identifier: NCT00527618     History of Changes
Other Study ID Numbers: 31203-D, GSK VAL111009 - VAL140
Study First Received: September 7, 2007
Results First Received: June 26, 2012
Last Updated: January 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Washington:
Herpes Simplex Virus Type 2
Human Immunodeficiency Virus
Treatment Naive

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

ClinicalTrials.gov processed this record on April 16, 2014