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Can Valacyclovir Delay the Need for Initiation of Human Immunodeficiency Virus (HIV) Treatment in HIV-infected Individuals? (VALIDATE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by University Health Network, Toronto
Sponsor:
Collaborator:
CIHR Canadian HIV Trials Network
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00860977
First received: March 11, 2009
Last updated: October 6, 2014
Last verified: October 2014
  Purpose

This study is a multicentre, randomized, placebo-controlled, fully blinded, clinical trial of twice daily oral valacyclovir 500mg versus placebo with the goal of delaying the need for initiating HAART among HIV infected individuals who neither use nor require HAART, and who have not used chronic suppressive anti-HSV therapy for at least the 6 months prior to study initiation.


Condition Intervention Phase
HIV Infection
Herpes Simplex Type II
HIV Infections
Drug: valacyclovir
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: VALacyclovir In Delaying Antiretroviral Treatment Entry

Resource links provided by NLM:


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

Primary Outcome Measures:
  • annual rate of change in CD4 count, calculated as the slope of participants' CD4 count change / time. [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • time from baseline until reaching the 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: up to 5 years ] [ Designated as safety issue: No ]
  • Annual rate of change in the CD4 cell count percentage, calculated as the slope of the participants' CD4 count percentage change over time [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Log10 plasma HIV viral load at 12, 24 and 36 months of follow-up [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Treatment-emergent adverse events and laboratory abnormalities (CBC, serum creatinine) [ Time Frame: up to 5 years ] [ Designated as safety issue: Yes ]
  • Frequency of episodes of HSV reactivations at any anatomic site [ Time Frame: up to 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: up to 5 years ] [ Designated as safety issue: No ]
  • Overall quality of life as measured by the MOS-HIV questionnaire at each 6-monthly time point [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • analysis of inflammatory markers in HIV disease progression, HIV Resistance Mutations and other herpesvirus serologies [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
  • genetic testing of HLA-B*5701 and HLA-B*5703 status, and future genetic markers related to HIV disease progression and the impact of herpes and valacyclovir [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 230
Study Start Date: March 2010
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
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
Experimental: Valacyclovir
oral valacyclovir 500mg twice daily
Drug: valacyclovir
oral valacyclovir 500mg twice daily
Other Name: Valtrex

  Eligibility

Ages Eligible for Study:   18 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 (determined by EIA and Western blot, sites' standard assays are acceptable if approved in advance by the PIs for the study, Dr. Darrell Tan and/or Dr. Sharon Walmsley)
  • 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 30 days of initiating trial (baseline visit)
  • 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 (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.)
  • Estimated creatinine clearance <30 mL/min
  • Other medical condition likely to cause death within 24 months
  • Enrolled in a therapeutic HIV vaccine or immunotherapy trial
  • Enrolled in another trial investigating the impact of another intervention on HIV disease progression
  • HIV elite controller (EC), phenotypically defined here as documented duration of HIV infection of ≥5 years, a persistent CD4 cell count ≥500 cells/mm3, and a persistent plasma HIV viral load of <1000 copies/mL in the absence of antiretroviral therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Recruiting
Buenos Aires, Argentina, C1202ABB
Contact: Pedro Cahn, MD    5411 49817777      
Principal Investigator: Pedro Cahn, MD         
Brazil
Instituto de Pesquisa Clínica Evandro Chagas Recruiting
Rio de Janeiro, Brazil
Principal Investigator: Beatriz Grinsztejn, MD PhD         
Ambulatorio de Infectologia da UNIFESP Recruiting
Sao Paulo, Brazil, 04040-002
Centro de Referencia e Treinamento em DST/AIDS Recruiting
Sao Paulo, Brazil, 04121-000
Canada, Alberta
University of Alberta Completed
Edmonton, Alberta, Canada, T6G 2C8
Canada, British Columbia
B.C. Women's Hospital & Health Centre - Oak Tree Clinic Recruiting
Vancouver, British Columbia, Canada, V6H 1N1
Vancouver Infectious Disease Clinic Recruiting
Vancouver, British Columbia, Canada, V6Z 2C7
Contact: Brian Conway, MD    604 642 6429      
Principal Investigator: Brian Conway, MD         
Cool Aid Community Health Centre Recruiting
VIctoria, British Columbia, Canada, V8W 1M8
Contact: Chris Fraser, MD    250-385-1466      
Principal Investigator: Chris Fraser, MD         
Canada, Nova Scotia
CDHA, QEII Health Sciences Centre Completed
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
McMaster University Health Sciences Centre Recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: Fiona Smaill, MD    905-521-2100 ext. 76332      
Principal Investigator: Fiona Smaill, MD         
The Ottawa Hospital, General Campus Divsions of Infectious Diseases Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Bill Cameron, MD    613-737-8902      
Principal Investigator: Bill Cameron, MD         
University of Ottawa Health Services Completed
Ottawa, Ontario, Canada, K1N 6N5
Sunnybrook Health Science Centre Recruiting
Toronto, Ontario, Canada, M2N 3M5
Contact: Anita Rachlis, MD    416-480-4689      
Principal Investigator: Anita Rachlis, MD         
St. Clair Medical Associates Completed
Toronto, Ontario, Canada, M4K 1N1
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Darrell Tan, MD    416-864-5568      
Principal Investigator: Darrell Tan, MD         
Maple Leaf Medical Clinic Recruiting
Toronto, Ontario, Canada, M5B 1L6
Contact: Jason Brunetta    416-465-0856      
Principal Investigator: Jason Brunetta, MD         
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Sharon L Walmsley, MD FRCPC    416-340-4800 ext 3871    sharon.walmsley@uhn.on.ca   
Contact: Darrell HS Tan, MD FRCPC    416-340-4800 ext 2240      
Sub-Investigator: Darrell HS Tan, MD FRCPC         
Principal Investigator: Sharon L Walmsley, MD         
Windsor Regional Hospital Completed
Windsor, Ontario, Canada, N8W 1E3
Canada, Quebec
Montreal Chest Institute Recruiting
Montreal, Quebec, Canada, H2X 2P4
Contact: Marina Klein, MD    514-843-2090      
Principal Investigator: Marina Klein, MD         
Centre Hospitalier de l'Université de Montréal Completed
Montréal, Quebec, Canada, H2L 4M1
Canada
Centre Hospitalier Universitaire de Quebec-Pavillon CHUL Recruiting
Quebec, Canada, G1V 4G2
Contact: Sylvie Trottier, MD    418-654-2705      
Principal Investigator: Sylvie Trottier, MD         
United Kingdom
Brighton & Sussex University Hospitals NHS Trust Recruiting
Brighton, United Kingdom, BN2 1ES
Guy's and St. Thomas' NHS Foundation Trust Recruiting
London, United Kingdom, SE1 7EH
St. Mary's Hospital Recruiting
London, United Kingdom, W2 1NY
St. Stephen's AIDS Trust Recruiting
London, United Kingdom, SW10 9NH
Sponsors and Collaborators
University Health Network, Toronto
CIHR Canadian HIV Trials Network
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:
Publications:
Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00860977     History of Changes
Other Study ID Numbers: CTN 240, ISRCTN66756285
Study First Received: March 11, 2009
Last Updated: October 6, 2014
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
HIV
Herpes simplex virus type II
Genital herpes
Treatment Naive

Additional relevant MeSH terms:
Herpes Simplex
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Infection
DNA Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Skin Diseases
Skin Diseases, Infectious
Skin Diseases, Viral
Slow Virus Diseases
Virus Diseases
Acyclovir
Valacyclovir
Anti-Infective Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014