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

NCT ID: NCT01176409

Last Updated: 2016-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2013-08-31

Brief 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.

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.

Conditions

Human Immunodeficiency Virus; Herpes Simplex

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High dose valacyclovir

Valacyclovir 1g po BID

Group Type: EXPERIMENTAL

Valacyclovir

Intervention Type: DRUG

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.

Low dose valacyclovir

Valacyclovir 500mg po BID

Group Type: ACTIVE_COMPARATOR

Valacyclovir

Intervention Type: DRUG

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

Inert placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Apo-Valacycyclovir; Valtrex

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Toronto

OTHER

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darrell HS Tan, MD FRCPC

Role: PRINCIPAL_INVESTIGATOR

University Health Network, University of Toronto

Sharon L Walmsley, MD FRCPC MSc

Role: PRINCIPAL_INVESTIGATOR

University Health Network, University of Toronto

Locations

Toronto General Hospital, University Health Network

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 23946220 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/23946220

Study Results

Other Identifiers

VALIANT-001

Identifier Type: -

Identifier Source: org_study_id