Can Valacyclovir Attenuate Inflammation in Antiretroviral-Treated HIV-Infected Individuals With Herpes Simplex Virus Type 2? (VALIANT Pilot)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2010 by University Health Network, Toronto.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
University of Toronto
Canadian Institutes of Health Research (CIHR)
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01176409
First received: August 4, 2010
Last updated: December 22, 2010
Last verified: December 2010

August 4, 2010
December 22, 2010
September 2010
June 2011   (final data collection date for primary outcome measure)
Percentage activated CD8+ T-cells [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percentage of CD8+ T-cells co-expressing CD38 and HLA-DR
Same as current
Complete list of historical versions of study NCT01176409 on ClinicalTrials.gov Archive Site
  • Inflammatory markers [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    IL-6, hsCRP, sICAM-1, LPS
  • CD4 cell count [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    CD4 cell count (absolute and percentage)
  • Virologic blips [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Plasma HIV RNA level >50 copies/mL but <1000 copies/mL, followed by a repeat plasma HIV RNA level <50 copies/mL.
  • Drug-related adverse events [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    Adverse events (AEs) are defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study medication. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not it is related to the medication.
  • HSV reactivations [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Clinical reactivations of herpes simplex virus. Simultaneous reactivations at more than one anatomic site will be counted as a single reactivation event.
  • Acyclovir-resistant HSV [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    Clinical reactivations of herpes simplex virus that are microbiologically confirmed to be caused by acyclovir-resistant virus.
Same as current
Not Provided
Not Provided
 
Can Valacyclovir Attenuate Inflammation in Antiretroviral-Treated HIV-Infected Individuals With Herpes Simplex Virus Type 2?
VALacyclovir for Inflammation AttenuatioN Trial Pilot (VALIANT Pilot)

The purpose of this study is to compare the levels of immune and inflammatory markers among HIV-1, HSV-2 co-infected adults achieving plasma HIV RNA suppression to <50 copies/mL, between those randomized to valacyclovir and placebo, over a twelve-week intervention period.

Highly active antiretroviral therapy (HAART) has dramatically reduced HIV-1 infection (herein referred to as 'HIV') related morbidity and mortality, transforming an invariably fatal disease into a manageable, chronic condition. Yet even HAART-treated HIV infection is characterized by chronic systemic inflammation and immune activation. This systemic inflammatory response is composed of multiple components, and can be quantified by measuring markers of immune activation, inflammatory cytokines, acute phase reactants, endothelial activation markers, and markers of microbial translocation. This inflammation is clinically relevant, as it may contribute directly to HIV disease progression and non-AIDS related morbidity and mortality in HIV-infected patients. Because this inflammation persists even in the context of suppressive HAART, albeit at modestly decreased levels, adjunctive therapeutic strategies to attenuate this persistent inflammatory response are therefore needed. Herpes simplex virus type 2 is a common, clinically important co-infection seen in individuals living with HIV infection, and may contribute to this ongoing inflammation. This pilot trial will investigate whether short-term valacyclovir for HSV-2 suppression can decrease systemic inflammation in HAART-treated, HIV-1, HSV-2 co-infected individuals.

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 Infections
  • Herpes Simplex
  • Drug: Valacyclovir
    Valacyclovir will be used at two different dosages (1g po BID and 500mg po BID) to be used for 12 weeks. Supplied as 500mg caplets.
    Other Names:
    • Apo-Valacycyclovir
    • Valtrex
  • Drug: Placebo
    Placebo, supplied as caplets identical in appearance, odour and taste to valacyclovir 500mg caplets.
  • Experimental: High dose valacyclovir
    Valacyclovir 1g po BID
    Intervention: Drug: Valacyclovir
  • Active Comparator: Low dose valacyclovir
    Valacyclovir 500mg po BID
    Intervention: Drug: Valacyclovir
  • Placebo Comparator: Placebo
    Inert placebo
    Intervention: Drug: Placebo
Yi TJ, Walmsley S, Szadkowski L, Raboud J, Rajwans N, Shannon B, Kumar S, Kain KC, Kaul R, Tan DH. A randomized controlled pilot trial of valacyclovir for attenuating inflammation and immune activation in HIV/herpes simplex virus 2-coinfected adults on suppressive antiretroviral therapy. Clin Infect Dis. 2013 Nov;57(9):1331-8. doi: 10.1093/cid/cit539. Epub 2013 Aug 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
September 2011
June 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • adult (aged 18 years or older)
  • documented HIV-1 infection (determined by EIA and Western blot)
  • documented HSV-2 seropositivity (determined by ELISA during screening)
  • no use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
  • sustained plasma HIV RNA<50 copies/mL on HAART for at least 12 months
  • no active opportunistic infection for at least 12 months

Exclusion Criteria:

  • hepatitis C co-infection
  • hepatitis B co-infection
  • 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 any other interventional clinical trial
Both
18 Years to 65 Years
No
Contact: Darrell H.S. Tan, MD FRCPC 416-340-5077 darrell.tan@gmail.com
Contact: Sharon L Walmsley, MD FRCPC MSc 416-340-3871
Canada
 
NCT01176409
VALIANT-001
No
Sharon Walmsley, University Health Network
University Health Network, Toronto
  • University of Toronto
  • Canadian Institutes of Health Research (CIHR)
Principal Investigator: Darrell H.S. Tan, MD FRCPC University Health Network, University of Toronto
Principal Investigator: Sharon L Walmsley, MD FRCPC MSc University Health Network, University of 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