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

University Health Network, Toronto

Status and phase: Completed; Phase 3

Conditions: Herpes Simplex; Human Immunodeficiency Virus

Treatments: Drug: Placebo; Drug: Valacyclovir

Study type: Interventional

Funder types: Other

Identifiers

NCT01176409

VALIANT-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 3 patient groups, including a placebo group

High dose valacyclovir

Experimental group

Description:

Valacyclovir 1g po BID

Treatment:

Drug: Valacyclovir

Low dose valacyclovir

Active Comparator group

Description:

Valacyclovir 500mg po BID

Treatment:

Drug: Valacyclovir

Placebo

Placebo Comparator group

Description:

Inert placebo

Treatment:

Drug: Placebo