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

NCT00860977 | Completed Phase 3 DMC

• 2 other identifiers: CTN 240ISRCTN66756285
• Study Type: interventional
• Target: 202
• Locations: 4 countries
• Sites: 25

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.

Conditions

HIV Infection; Herpes Simplex Type II; HIV Infections

Keywords

HIV; Herpes simplex virus type II; Genital herpes; Treatment Naive

Outcome Measures

Primary Outcomes (1)

• annual rate of change in CD4 count, calculated as the slope of participants' CD4 count change / time.

  up to 5 years

Secondary Outcomes (7)

• 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

• 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

• Treatment-emergent adverse events and laboratory abnormalities (CBC, serum creatinine)

  up to 5 years

• Frequency of episodes of HSV reactivations at any anatomic site

  up to 5 years

Other Outcomes (2)

• analysis of inflammatory markers in HIV disease progression, HIV Resistance Mutations and other herpesvirus serologies

  up to 6 years

• 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

  up to 5 years

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily

Drug: Placebo

Valacyclovir

EXPERIMENTAL

oral valacyclovir 500mg twice daily

Drug: valacyclovir

Interventions

valacyclovir DRUG

oral valacyclovir 500mg twice daily

Also known as: Valtrex

Valacyclovir

Placebo DRUG

Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• CIHR Canadian HIV Trials Network: collaborator

Study Sites (25)

Fundación Huesped

Buenos Aires, C1202ABB, Argentina

Location

Instituto de Pesquisa Clínica Evandro Chagas

Rio de Janeiro, Brazil

Location

Ambulatorio de Infectologia da UNIFESP

São Paulo, 04040-002, Brazil

Location

Centro de Referencia e Treinamento em DST/AIDS

São Paulo, 04121-000, Brazil

Location

University of Alberta

Edmonton, Alberta, T6G 2C8, Canada

Location

B.C. Women's Hospital & Health Centre - Oak Tree Clinic

Vancouver, British Columbia, V6H 1N1, Canada

Location

Vancouver Infectious Disease Clinic

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Cool Aid Community Health Centre

Victoria, British Columbia, V8W 1M8, Canada

Location

CDHA, QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

McMaster University Health Sciences Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

The Ottawa Hospital, General Campus Divsions of Infectious Diseases

Ottawa, Ontario, K1H 8L6, Canada

Location

University of Ottawa Health Services

Ottawa, Ontario, K1N 6N5, Canada

Location

Sunnybrook Health Science Centre

Toronto, Ontario, M2N 3M5, Canada

Location

St. Clair Medical Associates

Toronto, Ontario, M4K 1N1, Canada

Location

Maple Leaf Medical Clinic

Toronto, Ontario, M5B 1L6, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

University Health Network

Toronto, Ontario, M5G 2N2, Canada

Location

Windsor Regional Hospital

Windsor, Ontario, N8W 1E3, Canada

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2L 4M1, Canada

Location

Montreal Chest Institute

Montreal, Quebec, H2X 2P4, Canada

Location

Centre Hospitalier Universitaire de Quebec-Pavillon CHUL

Québec, G1V 4G2, Canada

Location

Brighton & Sussex University Hospitals NHS Trust

Brighton, BN2 1ES, United Kingdom

Location

Guy's and St. Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

St. Stephen's AIDS Trust

London, SW10 9NH, United Kingdom

Location

St. Mary's Hospital

London, W2 1NY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 21106086 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Herpes Genitalis

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Herpes Simplex; Herpesviridae Infections; DNA Virus Infections; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Male; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sharon L Walmsley, MD FRCPC MSc

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Darrell HS Tan, MD FRCPC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2009
• First Posted: March 13, 2009
• Study Start: March 1, 2010
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: March 6, 2018

Record last verified: 2018-03

Locations

BR (3); GB (4); CA (17); AR (1)