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

This study has been completed.
University of Toronto
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
University Health Network, Toronto Identifier:
First received: August 4, 2010
Last updated: May 10, 2016
Last verified: May 2016
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.

Condition Intervention Phase
Human Immunodeficiency Virus
Herpes Simplex
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 for Inflammation AttenuatioN Trial Pilot (VALIANT Pilot)

Resource links provided by NLM:

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • 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

Secondary Outcome Measures:
  • 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.

Enrollment: 60
Study Start Date: September 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High dose valacyclovir
Valacyclovir 1g po BID
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
Active Comparator: Low dose valacyclovir
Valacyclovir 500mg po BID
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
Placebo Comparator: Placebo
Inert placebo
Drug: Placebo
Placebo, supplied as caplets identical in appearance, odour and taste to valacyclovir 500mg caplets.

Detailed Description:
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.

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01176409

Canada, Ontario
Toronto General Hospital, University Health Network
Toronto, Ontario, Canada, M5G 2N2
Sponsors and Collaborators
University Health Network, Toronto
University of Toronto
Canadian Institutes of Health Research (CIHR)
Principal Investigator: Darrell HS Tan, MD FRCPC University Health Network, University of Toronto
Principal Investigator: Sharon L Walmsley, MD FRCPC MSc University Health Network, University of Toronto
  More Information

Additional Information:
Responsible Party: University Health Network, Toronto Identifier: NCT01176409     History of Changes
Other Study ID Numbers: VALIANT-001 
Study First Received: August 4, 2010
Last Updated: May 10, 2016
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Herpes Simplex
Immunologic Deficiency Syndromes
DNA Virus Infections
Herpesviridae Infections
Immune System Diseases
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 processed this record on May 25, 2016