Clinical trial NCT01176409: Can Valacyclovir Attenuate Inflammation in Antiretroviral-Treated HIV-Infected Individuals With Herpes Simplex Virus Type 2?
Official title: VALacyclovir for Inflammation AttenuatioN Trial Pilot (VALIANT Pilot)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human Immunodeficiency Virus
Herpes Simplex
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: University of Toronto
name: Canadian Institutes of Health Research (CIHR)
First posted: 2010-08-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage activated CD8+ T-cells
timeFrame: 12 weeks
Secondary outcomes:
measure: Inflammatory markers
timeFrame: 12 weeks
measure: CD4 cell count
timeFrame: 12 weeks
measure: Virologic blips
timeFrame: 12 weeks
measure: Drug-related adverse events
timeFrame: 18 weeks
measure: HSV reactivations
timeFrame: 12 weeks
measure: Acyclovir-resistant HSV
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital, University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, University of Toronto
name: Darrell HS Tan, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, University of Toronto
name: Sharon L Walmsley, MD FRCPC MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.