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

March 11, 2009
October 6, 2014
March 2010
February 2016   (final data collection date for primary outcome measure)
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 ]
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 ]
Complete list of historical versions of study NCT00860977 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
  • 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 ]
Not Provided
 
Can Valacyclovir Delay the Need for Initiation of Human Immunodeficiency Virus (HIV) Treatment in HIV-infected Individuals?
VALacyclovir In Delaying Antiretroviral Treatment Entry

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • HIV Infection
  • Herpes Simplex Type II
  • HIV Infections
  • Drug: valacyclovir
    oral valacyclovir 500mg twice daily
    Other Name: Valtrex
  • Drug: Placebo
    Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily
  • Placebo Comparator: Placebo
    Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily
    Intervention: Drug: Placebo
  • Experimental: Valacyclovir
    oral valacyclovir 500mg twice daily
    Intervention: Drug: valacyclovir
Tan DH, Raboud JM, Kaul R, Grinsztejn B, Cahn P, Walmsley SL. Can herpes simplex virus type 2 suppression slow HIV disease progression: a study protocol for the VALacyclovir In Delaying Antiretroviral Treatment Entry (VALIDATE) trial. Trials. 2010 Nov 24;11:113. doi: 10.1186/1745-6215-11-113.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
230
February 2017
February 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
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
Brazil,   Canada,   United Kingdom,   Argentina
 
NCT00860977
CTN 240, ISRCTN66756285
Yes
University Health Network, Toronto
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
University Health Network, Toronto
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP