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
Results First Received: June 26, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Genital Herpes
HIV Infection
Interventions: Drug: valacyclovir
Drug: acyclovir

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
We recruited HIV-1/HSV-2 coinfected patients in Seattle, WA, between January 2008 and June 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 49 persons screened, 15 were found to be ineligible for reasons including lack of HSV-2 infection (n=5), plans to initiate ART (n=3), undetectable plasma HIV-1 RNA (n=3), neutropenia (n=2), elevated hepatic transaminases (n=1), and incarceration (n=1). The remaining 34 participants were randomized.

Reporting Groups
  Description
Acyclovir Followed by Valacyclovir Acyclovir 400 mg twice daily, followed by a two-week washout period, then valacyclovir 1000 mg twice daily
Valacyclovir Followed by Acyclovir Valacyclovir 1000 mg twice daily, followed by a two-week washout period, then acyclovir 400 mg twice daily

Participant Flow for 3 periods

Period 1:   Week 1-12 (First Intervention)
    Acyclovir Followed by Valacyclovir     Valacyclovir Followed by Acyclovir  
STARTED     16 [1]   18 [2]
COMPLETED     13 [1]   16 [3]
NOT COMPLETED     3     2  
Lost to Follow-up                 3                 1  
Adverse Event                 0                 1  
[1] Acyclovir
[2] Valacyclovir; one participant was removed from the study due to urticaria after 2.5 weeks
[3] Valacyclovir

Period 2:   Week 13-14 (Washout)
    Acyclovir Followed by Valacyclovir     Valacyclovir Followed by Acyclovir  
STARTED     13     16  
COMPLETED     12     16  
NOT COMPLETED     1     0  
Lost to Follow-up                 1                 0  

Period 3:   Week 15-18 (Second Intervention)
    Acyclovir Followed by Valacyclovir     Valacyclovir Followed by Acyclovir  
STARTED     12 [1]   16 [2]
COMPLETED     12 [1]   13 [2]
NOT COMPLETED     0     3  
Lost to Follow-up                 0                 1  
Censored on initiation of HAART                 0                 1  
Withdrawal by Subject                 0                 1  
[1] Valacyclovir
[2] Acyclovir



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Entire Study Population This includes all 34 participants who were randomized. A subset of 28 participants were included in the analysis since only 28 participants contributed samples on both arms of the crossover study.

Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
  34  
Age  
[units: Years]
Mean ( Full Range )
  43  
  ( 24 to 66 )  
Gender  
[units: participants]
 
Female     6  
Male     28  
Race/Ethnicity, Customized  
[units: participants]
 
Caucasian     23  
African-American     9  
Other     2  
CD4 Count  
[units: cells/microliter]
Mean ( Full Range )
  526  
  ( 73 to 1094 )  
Plasma HIV-1 RNA  
[units: log10┬ácopies/mL]
Mean ( Full Range )
  3.84  
  ( 1.17 to 6.93 )  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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) ]

2.  Primary:   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 ]

3.  Secondary:   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) ]

4.  Secondary:   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 ]

5.  Secondary:   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 ]

6.  Secondary:   The Safety of Valacyclovir 1 Gram Orally Twice Daily in HIV-1 Seropositive Persons.   [ Time Frame: 12 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Our findings are limited by the high loss to follow up, which is especially problematic in cross-over studies.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Tara Perti, MD
Organization: University of Washington, Virology Research Clinic
phone: (206) 520-4340
e-mail: tarap@u.washington.edu


No publications provided


Responsible Party: Jared Baeten, 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