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

This study is currently recruiting participants.
Verified December 2010 by University Health Network, Toronto
Sponsor:
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00860977
First received: March 11, 2009
Last updated: December 22, 2010
Last verified: December 2010
  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 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:
  • 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: March 2010
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (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

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 Active, not recruiting
Buenos Aires, Argentina, C1202ABB
Brazil
Instituto de Pesquisa Clínica Evandro Chagas Active, not recruiting
Rio de Janeiro, Brazil
Canada, Alberta
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2C8
Contact: Barbara Romanowski, MD    780-436-4900      
Principal Investigator: Barbara Romanowski, MD         
Canada, British Columbia
Downtown ID 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 Recruiting
Halifax, Nova Scotia, Canada, B3H 2Y9
Contact: David Haase, MD    902-473-7786      
Principal Investigator: David Haase, MD         
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         
University of Ottawa Health Services Recruiting
Ottawa, Ontario, Canada, K1N 6N5
Contact: Don Kilby, MD    613-654-3950      
Principal Investigator: Don Kilby, 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         
St. Michael's Hospital Active, not recruiting
Toronto, Ontario, Canada, M5B 1W8
St. Clair Medical Associates Recruiting
Toronto, Ontario, Canada, M4K 1N1
Contact: Ken Logue, MD    416- 966-0178      
Principal Investigator: Ken Logue, MD         
Sunnybrook Health Science Centre Recruiting
Toronto, Ontario, Canada, M2N 3M5
Contact: Anita Rachlis, MD    416-480-4689      
Principal Investigator: Anita Rachlis, 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         
Maple Leaf Medical Clinic Recruiting
Toronto, Ontario, Canada, M5B 1L6
Contact: Jason Brunetta    416-465-0856      
Principal Investigator: Jason Brunetta, MD         
Windsor Regional Hospital Recruiting
Windsor, Ontario, Canada, N8W 1E3
Contact: Jeffery Cohen, MD    519-254-6115      
Principal Investigator: Jeffery Cohen, MD         
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 Recruiting
Montréal, Quebec, Canada, H2L 4M1
Contact: Claude Fortin, MD    514 890 8000 Ext 24723      
Principal Investigator: Claude Fortin, MD         
Clinique Médicale du Quartier Latin Recruiting
Montréal, Quebec, Canada, H2L 5B1
Contact: Jean-Guy Baril, MD    514-285-2226      
Principal Investigator: Jean-Guy Baril, MD         
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         
Sponsors and Collaborators
University Health Network, Toronto
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: Dr Sharon Walmsley, Dr Darrell Tan, CIHR Canadian HIV Trials Network
ClinicalTrials.gov Identifier: NCT00860977     History of Changes
Other Study ID Numbers: CTN-240, ISRCTN66756285
Study First Received: March 11, 2009
Last Updated: December 22, 2010
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:
Acquired Immunodeficiency Syndrome
HIV Infections
Herpes Simplex
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Valacyclovir
Acyclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 14, 2014