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

HIV Infections Clinical Trial

— VALIANT Pilot  

Official title:

VALacyclovir for Inflammation AttenuatioN Trial Pilot (VALIANT Pilot)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01176409
• Other study ID #: VALIANT-001
• Status: Recruiting
• Phase: Phase 3
• First received: August 4, 2010
• Last updated: December 22, 2010
• Start date: September 2010
• Est. completion date: September 2011

Study information

• Verified date: December 2010
• Source: University Health Network, Toronto
• Contact: Darrell H.S. Tan, MD FRCPC
• Phone: 416-340-5077
• Email: darrell.tan[@]gmail.com
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Herpes Simplex
• HIV Infections

Intervention

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.
• Placebo
Placebo, supplied as caplets identical in appearance, odour and taste to valacyclovir 500mg caplets.

Locations

Country	Name	City	State
Canada	Toronto General Hospital, University Health Network	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
University Health Network, Toronto	Canadian Institutes of Health Research (CIHR), University of Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage activated CD8+ T-cells	Percentage of CD8+ T-cells co-expressing CD38 and HLA-DR	12 weeks	No
Secondary	Inflammatory markers	IL-6, hsCRP, sICAM-1, LPS	12 weeks	No
Secondary	CD4 cell count	CD4 cell count (absolute and percentage)	12 weeks	No
Secondary	Virologic blips	Plasma HIV RNA level >50 copies/mL but <1000 copies/mL, followed by a repeat plasma HIV RNA level <50 copies/mL.	12 weeks	No
Secondary	Drug-related adverse events	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.	18 weeks	Yes
Secondary	HSV reactivations	Clinical reactivations of herpes simplex virus. Simultaneous reactivations at more than one anatomic site will be counted as a single reactivation event.	12 weeks	No
Secondary	Acyclovir-resistant HSV	Clinical reactivations of herpes simplex virus that are microbiologically confirmed to be caused by acyclovir-resistant virus.	18 weeks	No

External Links

•   University Health Network Immunodeficiency Clinic Website