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

University Health Network, Toronto60 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Human Immunodeficiency Virus Herpes Simplex

Interventions

ValacyclovirDRUG

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.

PlaceboDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

Toronto General Hospital, University Health Network

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

Percentage activated CD8+ T-cells

Percentage of CD8+ T-cells co-expressing CD38 and HLA-DR

Time frame: 12 weeks

Secondary Outcomes

Inflammatory markers

IL-6, hsCRP, sICAM-1, LPS

Time frame: 12 weeks

CD4 cell count

CD4 cell count (absolute and percentage)

Time frame: 12 weeks

Virologic blips

Plasma HIV RNA level \>50 copies/mL but \<1000 copies/mL, followed by a repeat plasma HIV RNA level \<50 copies/mL.

Time frame: 12 weeks

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.

Time frame: 18 weeks

HSV reactivations

Clinical reactivations of herpes simplex virus. Simultaneous reactivations at more than one anatomic site will be counted as a single reactivation event.

Time frame: 12 weeks

Acyclovir-resistant HSV

Clinical reactivations of herpes simplex virus that are microbiologically confirmed to be caused by acyclovir-resistant virus.

Time frame: 18 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.