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

NCT ID: NCT00527618

Last Updated: 2018-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2011-03-31

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.

Conditions

Genital Herpes; HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard-dose acyclovir

acyclovir 400 mg orally twice daily for 12 weeks.

Group Type: ACTIVE_COMPARATOR

acyclovir

Intervention Type: DRUG

acyclovir 400 mg orally twice daily for 12 weeks.

High-dose valacyclovir

valacyclovir 1000 mg orally twice daily for 12 weeks.

Group Type: EXPERIMENTAL

valacyclovir

Intervention Type: DRUG

valacyclovir 1000 mg orally twice daily for 12 weeks.

Interventions

valacyclovir

valacyclovir 1000 mg orally twice daily for 12 weeks.

Intervention Type: DRUG

acyclovir

acyclovir 400 mg orally twice daily for 12 weeks.

Intervention Type: DRUG

Other Intervention Names

Valtrex; Zovirax

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Jared Baeten

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jared Baeten, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Anna Wald, MD, MPH

Role: STUDY_DIRECTOR

University of Washington

Locations

University of Washington Virology Research Clinic

Seattle, Washington, United States

Countries

United States

Other Identifiers

GSK VAL111009 - VAL140

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

31203

Identifier Type: -

Identifier Source: org_study_id