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. (see Contacts and Locations)
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

March 11, 2009
December 22, 2010
March 2010
February 2015   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00860977 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
Not Provided
Not Provided
 
Can Valacyclovir Delay the Need for Initiation of Human Immunodeficiency Virus (HIV) Treatment in HIV-infected Individuals With Herpes Simplex Virus Type 2?
VALacyclovir In Delaying Antiretroviral Treatment Entry

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.

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.

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
  • Herpesvirus 2, Human
  • 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
480
February 2015
February 2015   (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
  • 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
Both
16 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
Argentina,   Brazil,   Canada
 
NCT00860977
CTN-240, ISRCTN66756285
Yes
Dr Sharon Walmsley, Dr Darrell Tan, CIHR Canadian HIV Trials Network
University Health Network, Toronto
Not Provided
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
December 2010

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