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

May 4, 2018 updated by: Jared Baeten, University of Washington

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98122
        • University of Washington Virology Research Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Valtrex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
26 weeks (12 weeks per drug intervention)
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
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.
The first four weeks of each intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
26 weeks (12 weeks per drug intervention)
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
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 first four weeks of each intervention
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
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.
72 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

GlaxoSmithKline

Investigators

  • Study Director: Anna Wald, MD, MPH, University of Washington

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (ACTUAL)

March 1, 2011

Study Completion (ACTUAL)

March 1, 2011

Study Registration Dates

First Submitted

September 7, 2007

First Submitted That Met QC Criteria

September 10, 2007

First Posted (ESTIMATE)

September 11, 2007

Study Record Updates

Last Update Posted (ACTUAL)

June 7, 2018

Last Update Submitted That Met QC Criteria

May 4, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 31203
  • GSK VAL111009 - VAL140 (OTHER_GRANT: GlaxoSmithKline)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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