Trial to Study the Effect of Dose of Herpes Simplex Virus-2 (HSV-2) Suppressive Therapy on HSV and HIV
Information source: University of Washington
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Genital Herpes; HIV Infection
Intervention: valacyclovir (Drug); acyclovir (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: University of Washington Official(s) and/or principal investigator(s): Jared Baeten, MD, PhD, Principal Investigator, Affiliation: University of Washington Anna Wald, MD, MPH, Study Director, Affiliation: University of Washington
Summary
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The Quantity of HIV-1 RNA in Plasma While on 400 mg Twice Daily of Acyclovir Versus 1000 mg Twice Daily of Valacyclovir.The Genital HSV Shedding Rate While on 400 mg Twice Daily of Acyclovir Versus 1000 mg Twice Daily of Valacyclovir.
Secondary outcome: The Effect of Valacyclovir 1 Gram Twice Daily Compared to Acyclovir 400 mg Twice Daily on the Percentage of Days With Genital Herpes Lesions.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. The Safety of Valacyclovir 1 Gram Orally Twice Daily in HIV-1 Seropositive Persons. Sub-Study: To Evaluate the Kinetics of Plasma HIV-1 Decline Over the First Three Days of High-dose Valacyclovir Administration.
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
University of Washington Virology Research Clinic, Seattle, Washington 98122, United States
Additional Information
Starting date: December 2007
Last updated: January 18, 2013
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