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

This study is ongoing, but not recruiting participants.
CIHR Canadian HIV Trials Network
Information provided by (Responsible Party):
University Health Network, Toronto Identifier:
First received: March 11, 2009
Last updated: September 21, 2015
Last verified: September 2015

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 ]

Enrollment: 202
Study Start Date: March 2010
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 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


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

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
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Please refer to this study by its identifier: NCT00860977

Fundación Huesped
Buenos Aires, Argentina, C1202ABB
Instituto de Pesquisa Clínica Evandro Chagas
Rio de Janeiro, Brazil
Ambulatorio de Infectologia da UNIFESP
Sao Paulo, Brazil, 04040-002
Centro de Referencia e Treinamento em DST/AIDS
Sao Paulo, Brazil, 04121-000
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2C8
Canada, British Columbia
B.C. Women's Hospital & Health Centre - Oak Tree Clinic
Vancouver, British Columbia, Canada, V6H 1N1
Vancouver Infectious Disease Clinic
Vancouver, British Columbia, Canada, V6Z 2C7
Cool Aid Community Health Centre
VIctoria, British Columbia, Canada, V8W 1M8
Canada, Nova Scotia
CDHA, QEII Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
McMaster University Health Sciences Centre
Hamilton, Ontario, Canada, L8N 3Z5
University of Ottawa Health Services
Ottawa, Ontario, Canada, K1N 6N5
The Ottawa Hospital, General Campus Divsions of Infectious Diseases
Ottawa, Ontario, Canada, K1H 8L6
University Health Network
Toronto, Ontario, Canada, M5G 2N2
Maple Leaf Medical Clinic
Toronto, Ontario, Canada, M5B 1L6
St. Clair Medical Associates
Toronto, Ontario, Canada, M4K 1N1
Sunnybrook Health Science Centre
Toronto, Ontario, Canada, M2N 3M5
St. Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8
Windsor Regional Hospital
Windsor, Ontario, Canada, N8W 1E3
Canada, Quebec
Montreal Chest Institute
Montreal, Quebec, Canada, H2X 2P4
Centre Hospitalier de l'Université de Montréal
Montréal, Quebec, Canada, H2L 4M1
Centre Hospitalier Universitaire de Quebec-Pavillon CHUL
Quebec, Canada, G1V 4G2
United Kingdom
Brighton & Sussex University Hospitals NHS Trust
Brighton, United Kingdom, BN2 1ES
Guy's and St. Thomas' NHS Foundation Trust
London, United Kingdom, SE1 7EH
St. Mary's Hospital
London, United Kingdom, W2 1NY
St. Stephen's AIDS Trust
London, United Kingdom, SW10 9NH
Sponsors and Collaborators
University Health Network, Toronto
CIHR Canadian HIV Trials Network
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:
Responsible Party: University Health Network, Toronto Identifier: NCT00860977     History of Changes
Other Study ID Numbers: CTN 240, ISRCTN66756285
Study First Received: March 11, 2009
Last Updated: September 21, 2015
Health Authority: Canada: Health Canada

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

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Herpes Simplex
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
Anti-Infective Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses processed this record on October 13, 2015