Clinical trial NCT00527618: Trial to Study the Effect of Dose of Herpes Simplex Virus-2 (HSV-2) Suppressive Therapy on HSV and HIV
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Genital Herpes
HIV Infection
Keywords: Herpes Simplex Virus Type 2
Human Immunodeficiency Virus
Treatment Naive
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2007-09-11
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: The Quantity of HIV-1 RNA in Plasma While on 400 mg Twice Daily of Acyclovir Versus 1000 mg Twice Daily of Valacyclovir.
timeFrame: 26 weeks (12 weeks per drug intervention)
measure: The Genital HSV Shedding Rate While on 400 mg Twice Daily of Acyclovir Versus 1000 mg Twice Daily of Valacyclovir.
timeFrame: The first four weeks of each intervention
Secondary outcomes:
measure: The Effect of Valacyclovir 1 Gram Twice Daily Compared to Acyclovir 400 mg Twice Daily on the Percentage of Days With Genital Herpes Lesions.
timeFrame: 26 weeks (12 weeks per drug intervention)
measure: 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.
timeFrame: The first four weeks of each intervention
measure: Sub-Study: To Evaluate the Kinetics of Plasma HIV-1 Decline Over the First Three Days of High-dose Valacyclovir Administration.
timeFrame: 72 hours
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington Virology Research Clinic
state: Washington
Study officials:
affiliation: University of Washington
name: Jared Baeten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Anna Wald, MD, MPH
role: STUDY_DIRECTOR
References: