Can Valaciclovir delay the need for initiation of human immunodeficiency virus (HIV) treatment in HIV – infected individuals

ISRCTN	ISRCTN66756285
DOI	https://doi.org/10.1186/ISRCTN66756285
ClinicalTrials.gov (NCT)	NCT00860977
Protocol serial number	MCT-94245
Sponsor	University Health Network (UHN) (Canada)
Funder	Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-94245)

Submission date: 06/03/2009
Registration date: 09/03/2009
Last edited: 16/04/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Sharon Walmsley
Scientific

Toronto General Hospital
200 Elizabeth Street
13EN Room 218
Toronto, Ontario
M5G 2C4
Canada

Phone	+1 416 340 3871
Email	sharon.walmsley@uhn.on.ca

Study information

Primary study design	Interventional
Study design	Multicentre randomised placebo-controlled fully blinded clinical trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Valaciclovir in delaying antiretroviral treatment entry: a multicentre, randomised, placebo-controlled, fully blinded clinical trial
Study acronym	VALIDATE
Study objectives	As or 17-12-2012, the title changed to “Can Valaciclovir delay the need for initiation of human immunodeficiency virus (HIV) treatment in HIV – infected individuals” As of 10/09/2010 a rollover (off treatment) period was added and the overall trial end date was updated to 01/03/2016 As of 21/09/2015 the overall trial end date has been updated from 01/03/2015 to 30/09/2016 and the recruitment end date has been updated from 01/03/2015 to 11/08/2015. As of 09/03/2010 this trial has now started to actively recruit participants. The anticipated trial dates of this record have been updated to reflect this; all changes can be found in the relevant fields. The previous anticipated start and end dates were as follows: Previous anticipated start date: 31/10/2009 Previous anticipated end date: 31/10/2015 As of 18/08/2009 this record has been extensively updated; all updates can be found under the relevant field with the above update date. Please also note that at this time, the anticipated start and end dates of this trial have also been updated; the initial anticipated start and end dates were: Initial anticipated start date: 01/05/2009 Initial anticipated end date: 30/04/2015 At this time, Argentina was also added as a country of recruitment, and the Sponsor was updated (initial sponsor at the time of registration was Canadian HIV Trials Network (CTN) (Canada)). Current hypothesis as of 18/08/2009: Valaciclovir 500 mg orally twice daily delays the time until highly active anti-retroviral therapy (HAART) is recommended or initiated among adults with both stable untreated human immunodeficiency virus (HIV) and herpes simplex virus (HSV) type 2 co-infection. Initial hypothesis at the time of registration: Valaciclovir 500 mg orally twice daily delays the time until highly active anti-retroviral therapy (HAART) is recommended or initiated among adults with both stable untreated human immunodeficiency virus (HIV) and infrequent or asymptomatic herpes simplex virus (HSV) type 2 co-infection.
Ethics approval(s)	Added 09/03/2010: University Health Network Research Ethics Board approved on the 22nd September 2009.
Health condition(s) or problem(s) studied	Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) co-infection
Intervention	Patients in the intervention group will receive oral valaciclovir 500 mg twice daily, the standard dose used for HSV-2 suppression in HIV-infected individuals. Individuals in the control arm will receive an odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily. The anticipated duration of follow-up for both arms of the trial is 3 - 5 years.
Intervention type	Drug
Phase	Phase IV
Drug / device / biological / vaccine name(s)	Valaciclovir
Primary outcome measure(s)	As or 17/12/2012 primary outcome changed to: Annual rate of change in CD4 count, calculated as the slope of patients' CD4 count change/time. Initial primary outcome measure: Time from baseline until reaching the primary endpoint: a composite of either a CD4 cell count less than or equal to 350 cells/mm^3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first.
Key secondary outcome measure(s)	1. Annual rate of change in CD4 count, calculated as the slope of patients' CD4 count change/time 2. Annual rate of change in the CD4 cell count percentage, calculated as the slope of the patient's CD4 count percentage change over time 3. Log^10 plasma HIV viral load at 12, 24 and 36 months of follow-up 4. Treatment-emergent adverse events and laboratory abnormalities (complete blood count [CBC], plasma creatinine, blood urea nitrogen, alanine transaminase, aspartate transaminase, total bilirubin, amylase, international normalised ratio, partial thromboplastin time) 5. Frequency of episodes of HSV reactivations at any anatomic site 6. Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed aciclovir-resistant HSV Added 18/08/2009: 7. Quality of life As of 17/12/2012 the first secondary outcome changed to: Time from baseline until reaching the primary endpoint: a composite of either a CD4 cell count less than or equal to 350 cells/mm^3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first.
Completion date	01/03/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	230
Key inclusion criteria	Current inclusion criteria as of 17/12/2012: 1. Adult (aged 18 years or older or as per Local/Provincial Guidelines), either sex, with documented HIV-1 infection 2. Documented HIV-1 infection (determined by EIA and Western blot) 3. No use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study 4. Anti-retroviral naive (no more than 14 days of total prior anti-retroviral [ARV] exposure) 5. 5. 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) 6. Does not meet recommendations for initiating ARV therapy according to current guidelines Initial inclusion criteria at the time of registration: 1. Adults aged over 18 years, either sex, with documented HIV-1 infection 2. Documented HSV-2 seropositivity 3. Maximum of two episodes recurrent symptomatic HSV recurrences per year by self-report 4. Neither currently using nor anticipated to require chronic anti-HSV therapy during the study 5. Anti-retroviral naive (no more than 14 days of total prior anti-retroviral [ARV] exposure) 6. CD4 count within the 400 - 900 cells/mm^3 range (inclusive) on two consecutive occasions, with at least one measurement within 4 weeks of initiating trial 7. Does not meet recommendations for initiating ARV therapy according to current guidelines
Key exclusion criteria	Current exclusion criteria as of 17/12/2012: 1. Pregnant or actively planning to become pregnant 2. Receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.) 3. Have an estimated creatinine clearance less than 30 ml/min 4. Have another medical condition likely to cause death within 24 months 5. Enrolled in a therapeutic HIV vaccine or immunotherapy trial 6. Enrolled in another trial investigating the impact of another intervention on HIV disease progression 7. 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 Initial exclusion criteria at the time of registration: 1. Pregnant 2. Receiving chemotherapy or chronic steroid therapy 3. Have an estimated creatinine clearance less than 30 ml/min 4. Have an active opportunistic infection 5. Have another medical condition likely to cause death within 24 months 6. Enrolled in a therapeutic vaccine or immunotherapy trial 7. Enrolled in another trial investigating the impact of another intervention on HIV disease progression 8. Fit the phenotype of an HIV elite controller (EC), since the natural history of HIV infection is fundamentally different in such individuals
Date of first enrolment	01/03/2010
Date of final enrolment	11/08/2015

Locations

Countries of recruitment

Argentina
Brazil
Canada

Study participating centre

Toronto General Hospital

Toronto, Ontario
M5G 2C4
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/02/2019		Yes	No
Protocol article	protocol	24/11/2010		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

16/04/2019: Publication reference added.