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

Phase 3

Completed

• Conditions: Human Immunodeficiency Virus; Herpes Simplex
• Interventions: Drug: Placebo; Drug: Valacyclovir

• Registration Number: NCT01176409
• Lead Sponsor: University Health Network, Toronto

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.

Study Timeline

• Study First Submitted: 2010-08-04
• Study First Submitted QC: 2010-08-04
• Study First Posted: 2010-08-06
• Study Start: 2010-09
• Primary Completion: 2013-08
• Study Completion: 2013-08
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-10
• Last Update Posted: 2016-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Inert placebo
Low dose valacyclovir	Valacyclovir	Valacyclovir 500mg po BID
High dose valacyclovir	Valacyclovir	Valacyclovir 1g po BID

Primary Outcome Measures

Name	Time	Method
Percentage activated CD8+ T-cells	12 weeks	Percentage of CD8+ T-cells co-expressing CD38 and HLA-DR

Secondary Outcome Measures

Name	Time	Method
CD4 cell count	12 weeks	CD4 cell count (absolute and percentage)
Inflammatory markers	12 weeks	IL-6, hsCRP, sICAM-1, LPS
Acyclovir-resistant HSV	18 weeks	Clinical reactivations of herpes simplex virus that are microbiologically confirmed to be caused by acyclovir-resistant virus.
Drug-related adverse events	18 weeks	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	12 weeks	Clinical reactivations of herpes simplex virus. Simultaneous reactivations at more than one anatomic site will be counted as a single reactivation event.
Virologic blips	12 weeks	Plasma HIV RNA level \>50 copies/mL but \<1000 copies/mL, followed by a repeat plasma HIV RNA level \<50 copies/mL.

Trial Locations

Locations (1)

Toronto General Hospital, University Health Network; 🇨🇦 Toronto, Ontario, Canada