Can Valacyclovir Delay the Need for Initiation of Human Immunodeficiency Virus (HIV) Treatment in HIV-infected Individuals?

Phase 3

Completed

• Conditions: HIV Infection; Herpes Simplex Type II; HIV Infections
• Interventions: Drug: valacyclovir; Drug: Placebo

• Registration Number: NCT00860977
• Lead Sponsor: University Health Network, Toronto

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-03-11
• Study First Submitted QC: 2009-03-11
• Study First Posted: 2009-03-13
• Study Start: 2010-03
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-02
• Last Update Posted: 2018-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 202

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Valacyclovir	valacyclovir	oral valacyclovir 500mg twice daily
Placebo	Placebo	Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily

Primary Outcome Measures

Name	Time	Method
annual rate of change in CD4 count, calculated as the slope of participants' CD4 count change / time.	up to 5 years

Secondary Outcome Measures

Name	Time	Method
Treatment-emergent adverse events and laboratory abnormalities (CBC, serum creatinine)	up to 5 years
Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed acyclovir-resistant HSV	up to 5 years
Annual rate of change in the CD4 cell count percentage, calculated as the slope of the participants' CD4 count percentage change over time	up to 5 years
Log10 plasma HIV viral load at 12, 24 and 36 months of follow-up	up to 5 years
Overall quality of life as measured by the MOS-HIV questionnaire at each 6-monthly time point	up to 5 years
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.	up to 5 years
Frequency of episodes of HSV reactivations at any anatomic site	up to 5 years

Trial Locations

Locations (25)

McMaster University Health Sciences Centre; 🇨🇦 Hamilton, Ontario, Canada

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

University of Ottawa Health Services; 🇨🇦 Ottawa, Ontario, Canada

Centro de Referencia e Treinamento em DST/AIDS; 🇧🇷 Sao Paulo, Brazil

St. Stephen's AIDS Trust; 🇬🇧 London, United Kingdom

Windsor Regional Hospital; 🇨🇦 Windsor, Ontario, Canada

Vancouver Infectious Disease Clinic; 🇨🇦 Vancouver, British Columbia, Canada

The Ottawa Hospital, General Campus Divsions of Infectious Diseases; 🇨🇦 Ottawa, Ontario, Canada

Instituto de Pesquisa Clínica Evandro Chagas; 🇧🇷 Rio de Janeiro, Brazil

Maple Leaf Medical Clinic; 🇨🇦 Toronto, Ontario, Canada

Guy's and St. Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom

Brighton & Sussex University Hospitals NHS Trust; 🇬🇧 Brighton, United Kingdom

St. Mary's Hospital; 🇬🇧 London, United Kingdom

Centre Hospitalier Universitaire de Quebec-Pavillon CHUL; 🇨🇦 Quebec, Canada

Sunnybrook Health Science Centre; 🇨🇦 Toronto, Ontario, Canada

St. Clair Medical Associates; 🇨🇦 Toronto, Ontario, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Montreal Chest Institute; 🇨🇦 Montreal, Quebec, Canada

CDHA, QEII Health Sciences Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Cool Aid Community Health Centre; 🇨🇦 VIctoria, British Columbia, Canada

Fundación Huesped; 🇦🇷 Buenos Aires, Argentina

University Health Network; 🇨🇦 Toronto, Ontario, Canada

B.C. Women's Hospital & Health Centre - Oak Tree Clinic; 🇨🇦 Vancouver, British Columbia, Canada

Centre Hospitalier de l'Université de Montréal; 🇨🇦 Montréal, Quebec, Canada

Ambulatorio de Infectologia da UNIFESP; 🇧🇷 Sao Paulo, Brazil