Can Valacyclovir Delay the Need for Initiation of Human Immunodeficiency Virus (HIV) Treatment in HIV-infected Individuals With Herpes Simplex Virus Type 2? - Full Text View

Sponsor:	University Health Network, Toronto
Collaborators:	Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz The Huesped Foundation
Information provided by:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00860977

Purpose

The purpose of this study is to determine whether medication to suppress herpes simplex virus type 2 (HSV-2) infection can slow the rate of HIV disease progression and delay the need for initiating HAART in HIV, HSV-2 co-infected individuals.

Condition	Intervention	Phase
HIV Infection Herpesvirus 2, Human HIV Infections	Drug: valacyclovir Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study
Official Title:	VALacyclovir In Delaying Antiretroviral Treatment Entry

Resource links provided by NLM:

MedlinePlus related topics: AIDS Herpes Simplex

Drug Information available for: Valaciclovir Valacyclovir hydrochloride

U.S. FDA Resources

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

Time from baseline until reaching the primary endpoint, a composite of either a CD4 cell count ≤350 cells/mm3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Annual rate of change in CD4 count, calculated as the slope of patients' CD4 count change / time [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Annual rate of change in the CD4 cell count percentage, calculated as the slope of the patient's CD4 count percentage change over time [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Log10 plasma HIV viral load [ Time Frame: 12, 24 and 36 months of follow-up ] [ Designated as safety issue: No ]
Treatment-emergent adverse events and laboratory abnormalities [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Frequency of episodes of HSV reactivations at any anatomic site [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed acyclovir-resistant HSV [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	480
Study Start Date:	January 2010
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo: Placebo Comparator Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily	Drug: Placebo Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily
Valacyclovir: Experimental oral valacyclovir 500mg twice daily	Drug: valacyclovir oral valacyclovir 500mg twice daily

Detailed Description:

Highly active antiretroviral therapy (HAART) has drastically reduced the morbidity and mortality associated with HIV infection, and transformed HIV from an invariably fatal disease into a manageable, chronic condition. However, the inconvenience, high cost, potential side effects, and significant risk of developing drug-resistant HIV associated with taking daily, lifelong HAART make the potential delay of HAART initiation an extremely desirable goal for HIV-infected individuals.

Suppression of herpes simplex virus (HSV)-2 co-infection may provide a novel therapeutic strategy for achieving this goal. HSV-2 is among the most common co-infections seen in persons infected with HIV, with rates of up to 52-95%. This co-infection is associated with increased blood levels of HIV, a major predictor of HIV disease progression, even when the person has no herpes symptoms. Medications such as valacyclovir that suppress herpes can also decrease blood levels of HIV, but the potential long-term clinical benefits of this drug have not been adequately studied. It is thus hypothesized that valacyclovir could slow HIV disease progression and prolong the period of time before a co-infected person needs to initiate HAART. This research has been designed to answer this important question through a randomized, placebo-controlled, multi-centre clinical trial.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

adult (aged 18 years or older or as per Local/Provincial Guidelines)
documented HIV-1 infection
documented HSV-2 seropositivity
no use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
antiretroviral naïve (no more than 14 days of total prior ARV exposure)
CD4 count within the 400-900 cells/mm3 range (inclusive) on two consecutive occasions, with at least one measurement within 4 weeks of initiating trial
does not meet recommendations for initiating ARV therapy according to current guidelines

Exclusion Criteria:

pregnancy or actively planning to become pregnant
receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications
estimated creatinine clearance <30 mL/min
medical condition likely to cause death within 24 months
enrolled in a therapeutic vaccine or immunotherapy trial
enrolled in another trial investigating the impact of another intervention on HIV disease progression
HIV elite controller / long-term non-progressor

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00860977

Contacts

Contact: Sharon L Walmsley, MD FRCPC MSc	416-340-4800 ext 3871	sharon.walmsley@uhn.on.ca
Contact: Darrell HS Tan, MD FRCPC	416-340-4800 ext 2240	darrell.tan@gmail.com

Locations

Argentina
Fundación Huesped
Buenos Aires, Argentina, C1202ABB
Brazil
Instituto de Pesquisa Clínica Evandro Chagas
Rio de Janeiro, Brazil
Canada
Centre Hospitalier Universitaire de Quebec-Pavillon CHUL
Quebec, Canada, G1V 4G2
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2C8
Canada, British Columbia
Downtown ID Clinic
Vancouver, British Columbia, Canada, V6Z 2C7
Canada, Nova Scotia
CDHA, QEII Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5G 2N2
Maple Leaf Medical Clinic
Toronto, Ontario, Canada, M5B 1L6
Windsor Regional Hospital
Windsor, Ontario, Canada, N8W 1E3
University of Ottawa Health Services
Ottawa, Ontario, Canada, K1N 6N5
St. Clair Medical Associates
Toronto, Ontario, Canada, M4K 1N1
Sunnybrook Health Science Centre
Toronto, Ontario, Canada, M2N 3M5
McMaster University Health Sciences Centre
Hamilton, Ontario, Canada, L8N 3Z5
St. Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8
Canada, Quebec
Centre Hospitalier de l'Université de Montréal
Montréal, Quebec, Canada, H2L 4M1
Montreal Chest Institute
Montreal, Quebec, Canada, H2X 2P4
Clinique Médicale du Quartier Latin
Montréal, Quebec, Canada, H2L 5B1
Université de Sherbrooke
Sherbrooke, Quebec, Canada, J1H 5N4
Clinique Médicale l'Actuel
Montréal, Quebec, Canada, H2L 4P9
McGill University Health Centre
Montreal, Quebec, Canada, H3G 1A4
Canada, Saskatchewan
Royal University Hospital
Saskatoon, Saskatchewan, Canada, S7N OW8

Sponsors and Collaborators

University Health Network, Toronto

Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz

The Huesped Foundation

Investigators

Principal Investigator:	Sharon L Walmsley, MD FRCPC MSc	University Health Network, Toronto
Principal Investigator:	Darrell HS Tan, MD FRCPC	University Health Network, Toronto

More Information

Additional Information:

CIHR Canadian HIV Trials Network homepage This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	CIHR Canadian HIV Trials Network ( Dr Sharon Walmsley, Dr Darrell Tan )
Study ID Numbers:	CTN-240, ISRCTN66756285
Study First Received:	March 11, 2009
Last Updated:	November 12, 2009
ClinicalTrials.gov Identifier:	NCT00860977 History of Changes
Health Authority:	Canada: Health Canada

Keywords provided by University Health Network, Toronto:

HIV
Herpes simplex virus type 2
Genital herpes
Treatment Naive

Additional relevant MeSH terms:

Communicable Diseases
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Infection
Valacyclovir
Therapeutic Uses
Retroviridae Infections
Herpes Simplex
RNA Virus Infections
Immune System Diseases
Skin Diseases
Acquired Immunodeficiency Syndrome

Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Herpesviridae Infections
Virus Diseases
Skin Diseases, Viral
Skin Diseases, Infectious
Acyclovir
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on February 08, 2010