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

NCT00527618 | Completed Phase 4 Results

• 2 other identifiers: 31203GSK VAL111009 - VAL140
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Genital Herpes; HIV Infection

Keywords

Herpes Simplex Virus Type 2; Human Immunodeficiency Virus; Treatment Naive

Outcome Measures

Primary Outcomes (2)

• The Quantity of HIV-1 RNA in Plasma While on 400 mg Twice Daily of Acyclovir Versus 1000 mg Twice Daily of Valacyclovir.

  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.

  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 Outcomes (3)

• The Effect of Valacyclovir 1 Gram Twice Daily Compared to Acyclovir 400 mg Twice Daily on the Percentage of Days With Genital Herpes Lesions.

  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.

  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.

  72 hours

Study Arms (2)

Standard-dose acyclovir

ACTIVE COMPARATOR

acyclovir 400 mg orally twice daily for 12 weeks.

Drug: acyclovir

High-dose valacyclovir

EXPERIMENTAL

valacyclovir 1000 mg orally twice daily for 12 weeks.

Drug: valacyclovir

Interventions

valacyclovir DRUG

valacyclovir 1000 mg orally twice daily for 12 weeks.

Also known as: Valtrex

High-dose valacyclovir

acyclovir DRUG

acyclovir 400 mg orally twice daily for 12 weeks.

Also known as: Zovirax

Standard-dose acyclovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

University of Washington Virology Research Clinic

Seattle, Washington, 98122, United States

Location

MeSH Terms

Conditions

Herpes Genitalis; HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Valacyclovir; Acyclovir

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; Herpes Simplex; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Blood-Borne Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Our findings are limited by the high loss to follow up, which is especially problematic in cross-over studies.

Results Point of Contact

• Title: Tara Perti, MD
• Organization: University of Washington, Virology Research Clinic

tarap@u.washington.edu

(206) 520-4340

Study Officials

• Jared Baeten, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

• Anna Wald, MD, MPH

  University of Washington

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 7, 2007
• First Posted: September 11, 2007
• Study Start: December 1, 2007
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: June 7, 2018
• Results First Posted: July 31, 2012

Record last verified: 2018-05

Locations

US (1)