Clinical trial NCT00860977: Can Valacyclovir Delay the Need for Initiation of Human Immunodeficiency Virus (HIV) Treatment in HIV-infected Individuals?
Official title: VALacyclovir In Delaying Antiretroviral Treatment Entry
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Herpes Simplex Type II
HIV Infections
Keywords: HIV
Herpes simplex virus type II
Genital herpes
Treatment Naive
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: CIHR Canadian HIV Trials Network
First posted: 2009-03-13
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a multicentre, randomized, placebo-controlled, fully blinded, clinical trial of twice daily oral valacyclovir 500mg versus placebo with the goal of delaying the need for initiating HAART among HIV infected individuals who neither use nor require HAART, and who have not used chronic suppressive anti-HSV therapy for at least the 6 months prior to study initiation.


Eligibility criteria: Inclusion Criteria:

* adult (aged 18 years or older or as per Local/Provincial Guidelines)
* documented HIV-1 infection (determined by EIA and Western blot, sites' standard assays are acceptable if approved in advance by the PIs for the study, Dr. Darrell Tan and/or Dr. Sharon Walmsley)
* no use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
* antiretroviral naïve (no more than 14 days of total prior ARV exposure)
* CD4 count within the 400-900 cells/mm3 range (inclusive) on two consecutive occasions, with at least one measurement within 30 days of initiating trial (baseline visit)
* does not meet recommendations for initiating ARV therapy according to current guidelines

Exclusion Criteria:

* 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 a therapeutic HIV vaccine or immunotherapy trial
* Enrolled in another trial investigating the impact of another intervention on HIV disease progression
* HIV elite controller (EC), phenotypically defined here as documented duration of HIV infection of ≥5 years, a persistent CD4 cell count ≥500 cells/mm3, and a persistent plasma HIV viral load of \<1000 copies/mL in the absence of antiretroviral therapy

Primary outcomes:
measure: annual rate of change in CD4 count, calculated as the slope of participants' CD4 count change / time.
timeFrame: up to 5 years
Secondary outcomes:
measure: time from baseline until reaching the composite of either a CD4 cell count ≤350 cells/mm3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first.
timeFrame: up to 5 years
measure: Annual rate of change in the CD4 cell count percentage, calculated as the slope of the participants' CD4 count percentage change over time
timeFrame: up to 5 years
measure: Log10 plasma HIV viral load at 12, 24 and 36 months of follow-up
timeFrame: up to 5 years
measure: Treatment-emergent adverse events and laboratory abnormalities (CBC, serum creatinine)
timeFrame: up to 5 years
measure: Frequency of episodes of HSV reactivations at any anatomic site
timeFrame: up to 5 years
measure: Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed acyclovir-resistant HSV
timeFrame: up to 5 years
measure: Overall quality of life as measured by the MOS-HIV questionnaire at each 6-monthly time point
timeFrame: up to 5 years
Other outcomes:
measure: analysis of inflammatory markers in HIV disease progression, HIV Resistance Mutations and other herpesvirus serologies
timeFrame: up to 6 years
measure: genetic testing of HLA-B*5701 and HLA-B*5703 status, and future genetic markers related to HIV disease progression and the impact of herpes and valacyclovir
timeFrame: up to 5 years
Locations:
city: Buenos Aires
country: Argentina
facility: Fundación Huesped
city: Rio de Janeiro
country: Brazil
facility: Instituto de Pesquisa Clínica Evandro Chagas
city: Sao Paulo
country: Brazil
facility: Ambulatorio de Infectologia da UNIFESP
city: Sao Paulo
country: Brazil
facility: Centro de Referencia e Treinamento em DST/AIDS
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: B.C. Women's Hospital & Health Centre - Oak Tree Clinic
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver Infectious Disease Clinic
state: British Columbia
city: VIctoria
country: Canada
facility: Cool Aid Community Health Centre
state: British Columbia
city: Halifax
country: Canada
facility: CDHA, QEII Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus Divsions of Infectious Diseases
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Health Services
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Clair Medical Associates
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Medical Clinic
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Chest Institute
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec-Pavillon CHUL
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: St. Stephen's AIDS Trust
city: London
country: United Kingdom
facility: St. Mary's Hospital
Study officials:
affiliation: University Health Network, Toronto
name: Sharon L Walmsley, MD FRCPC MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, Toronto
name: Darrell HS Tan, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tan DH, Raboud JM, Kaul R, Grinsztejn B, Cahn P, Walmsley SL. Can herpes simplex virus type 2 suppression slow HIV disease progression: a study protocol for the VALacyclovir In Delaying Antiretroviral Treatment Entry (VALIDATE) trial. Trials. 2010 Nov 24;11:113. doi: 10.1186/1745-6215-11-113.