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

Sponsor:	University of Washington
Collaborator:	GlaxoSmithKline
Information provided by (Responsible Party):	Jared Baeten, University of Washington
ClinicalTrials.gov Identifier:	NCT00527618

Purpose

To compare the effect of daily valacyclovir 1 gram orally twice daily versus acyclovir 400 mg orally twice daily on the frequency of genital HSV reactivation and on plasma and genital HIV-1 levels among HSV-2/HIV-1 co-infected individuals. The investigators hypothesize that both treatments will reduce genital HSV and systemic and genital HIV-1.

Condition	Intervention	Phase
Genital Herpes HIV Infections	Drug: valacyclovir Drug: acyclovir	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomized, Open-label, Crossover Trial of the Effect of Dosing of Daily HSV-2 Suppressive Therapy on HSV Reactivation and Plasma and Genital HIV-1 Levels Among HIV-1/ HSV-2 Co-infected Persons

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Genital Herpes HIV/AIDS Herpes Simplex

Drug Information available for: Acyclovir Acyclovir sodium Valaciclovir Valacyclovir hydrochloride

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

The primary endpoints are the presence and quantity of genital HSV and the level of HIV-1 RNA in plasma and genital secretions of participants while on 400 mg twice daily of acyclovir versus while on 1000 mg twice daily of valacyclovir. [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate the effect of valacyclovir 1 gram orally twice daily on prevention of days with genital herpes lesions compared with acyclovir 400 mg orally twice daily. [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
To evaluate the safety of valacyclovir 1 gram orally twice daily in HIV-1 seropositive persons. [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
Sub-Study A: To evaluate the effect of valacyclovir twice daily on plasma HIV-1 replication. [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	38
Study Start Date:	December 2007
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 valacyclovir 1 gram orally twice daily	Drug: valacyclovir 1 gram orally twice daily Other Name: Valtrex
Active Comparator: 2 acyclovir 400 mg orally twice daily	Drug: acyclovir 400 mg orally twice daily

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 detection. Each week during the entire study period, participants will provide plasma and genital samples for HIV-1 detection.

Open-label acyclovir and valacyclovir will be used for this trial, as the primary outcome measures (genital HSV and plasma and genital HIV-1) are unlikely to be influenced by knowledge of treatment assignment. However, laboratory staff performing plasma and genital HIV-1 measurements will not be aware of treatment assignment.

Optional Sub-Study A: Sub-study A will be offered to participants who are about to start the valacyclovir arm of the parent protocol. The purpose of sub-study A is to measure the effect of valacyclovir twice daily on plasma HIV-1 replication.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00527618

Locations

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

Sponsors and Collaborators

University of Washington

GlaxoSmithKline

Investigators

Principal Investigator:	Jared Baeten, MD, PhD	University of Washington
Study Director:	Anna Wald, MD, MPH	University of Washington

More Information

No publications provided

Responsible Party:	Jared Baeten, Principal Investigator, University of Washington
ClinicalTrials.gov Identifier:	NCT00527618 History of Changes
Other Study ID Numbers:	31203-D, GSK VAL111009 - VAL140
Study First Received:	September 7, 2007
Last Updated:	December 2, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Washington:

Herpes Simplex Virus 2
Human Immunodeficiency Virus
Treatment Naive

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Herpes Genitalis
Herpes Simplex
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

Herpesviridae Infections
DNA Virus Infections
Genital Diseases, Male
Genital Diseases, Female
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Acyclovir
Valacyclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012