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

HIV Infections Clinical Trial

— VALIDATE  

Official title:

VALacyclovir In Delaying Antiretroviral Treatment Entry

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00860977
• Other study ID #: CTN 240
• Secondary ID: ISRCTN66756285
• Status: Completed
• Phase: Phase 3
• First received: March 11, 2009
• Last updated: March 2, 2018
• Start date: March 2010
• Est. completion date: August 2015

Study information

• Verified date: March 2018
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• Herpes Simplex
• Herpes Simplex Type II
• HIV Infection
• HIV Infections
• Infection

Intervention

Drug:
• valacyclovir
oral valacyclovir 500mg twice daily
• Placebo
Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily

Locations

Country	Name	City	State
Argentina	Fundación Huesped	Buenos Aires
Brazil	Instituto de Pesquisa Clínica Evandro Chagas	Rio de Janeiro
Brazil	Ambulatorio de Infectologia da UNIFESP	Sao Paulo
Brazil	Centro de Referencia e Treinamento em DST/AIDS	Sao Paulo
Canada	University of Alberta	Edmonton	Alberta
Canada	CDHA, QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	McMaster University Health Sciences Centre	Hamilton	Ontario
Canada	Montreal Chest Institute	Montreal	Quebec
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec
Canada	The Ottawa Hospital, General Campus Divsions of Infectious Diseases	Ottawa	Ontario
Canada	University of Ottawa Health Services	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec-Pavillon CHUL	Quebec
Canada	Maple Leaf Medical Clinic	Toronto	Ontario
Canada	St. Clair Medical Associates	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Science Centre	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	B.C. Women's Hospital & Health Centre - Oak Tree Clinic	Vancouver	British Columbia
Canada	Vancouver Infectious Disease Clinic	Vancouver	British Columbia
Canada	Cool Aid Community Health Centre	VIctoria	British Columbia
Canada	Windsor Regional Hospital	Windsor	Ontario
United Kingdom	Brighton & Sussex University Hospitals NHS Trust	Brighton
United Kingdom	Guy's and St. Thomas' NHS Foundation Trust	London
United Kingdom	St. Mary's Hospital	London
United Kingdom	St. Stephen's AIDS Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	CIHR Canadian HIV Trials Network

Countries where clinical trial is conducted

Argentina,  Brazil,  Canada,  United Kingdom, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	analysis of inflammatory markers in HIV disease progression, HIV Resistance Mutations and other herpesvirus serologies		up to 6 years
Other	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
Primary	annual rate of change in CD4 count, calculated as the slope of participants' CD4 count change / time.		up to 5 years
Secondary	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
Secondary	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
Secondary	Log10 plasma HIV viral load at 12, 24 and 36 months of follow-up		up to 5 years
Secondary	Treatment-emergent adverse events and laboratory abnormalities (CBC, serum creatinine)		up to 5 years
Secondary	Frequency of episodes of HSV reactivations at any anatomic site		up to 5 years
Secondary	Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed acyclovir-resistant HSV		up to 5 years
Secondary	Overall quality of life as measured by the MOS-HIV questionnaire at each 6-monthly time point		up to 5 years

External Links

•   CIHR Canadian HIV Trials Network - CTN 240