Can Valacyclovir Delay the Need for Initiation of Human Immunodeficiency Virus (HIV) Treatment in HIV-infected Individuals With Herpes Simplex Virus Type 2? - Full Text View

Sponsor:	University Health Network, Toronto
Information provided by:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00860977

Purpose

The purpose of this study is to determine whether medication to suppress herpes simplex virus type 2 (HSV-2) infection can slow the rate of HIV disease progression and delay the need for initiating HAART in HIV, HSV-2 co-infected individuals.

Condition	Intervention	Phase
HIV Infection Herpesvirus 2, Human HIV Infections	Drug: valacyclovir Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	VALacyclovir In Delaying Antiretroviral Treatment Entry

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Herpes Simplex

Drug Information available for: Valaciclovir Valacyclovir hydrochloride

U.S. FDA Resources

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

Time from baseline until reaching the primary endpoint, a 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. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Annual rate of change in CD4 count, calculated as the slope of patients' CD4 count change / time [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Annual rate of change in the CD4 cell count percentage, calculated as the slope of the patient's CD4 count percentage change over time [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Log10 plasma HIV viral load [ Time Frame: 12, 24 and 36 months of follow-up ] [ Designated as safety issue: No ]
Treatment-emergent adverse events and laboratory abnormalities [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Frequency of episodes of HSV reactivations at any anatomic site [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed acyclovir-resistant HSV [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	480
Study Start Date:	March 2010
Estimated Study Completion Date:	February 2015
Estimated Primary Completion Date:	February 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily	Drug: Placebo Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily
Experimental: Valacyclovir oral valacyclovir 500mg twice daily	Drug: valacyclovir oral valacyclovir 500mg twice daily Other Name: Valtrex

Detailed Description:

Highly active antiretroviral therapy (HAART) has drastically reduced the morbidity and mortality associated with HIV infection, and transformed HIV from an invariably fatal disease into a manageable, chronic condition. However, the inconvenience, high cost, potential side effects, and significant risk of developing drug-resistant HIV associated with taking daily, lifelong HAART make the potential delay of HAART initiation an extremely desirable goal for HIV-infected individuals.

Suppression of herpes simplex virus (HSV)-2 co-infection may provide a novel therapeutic strategy for achieving this goal. HSV-2 is among the most common co-infections seen in persons infected with HIV, with rates of up to 52-95%. This co-infection is associated with increased blood levels of HIV, a major predictor of HIV disease progression, even when the person has no herpes symptoms. Medications such as valacyclovir that suppress herpes can also decrease blood levels of HIV, but the potential long-term clinical benefits of this drug have not been adequately studied. It is thus hypothesized that valacyclovir could slow HIV disease progression and prolong the period of time before a co-infected person needs to initiate HAART. This research has been designed to answer this important question through a randomized, placebo-controlled, multi-centre clinical trial.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

adult (aged 18 years or older or as per Local/Provincial Guidelines)
documented HIV-1 infection
documented HSV-2 seropositivity
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 4 weeks of initiating trial
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
estimated creatinine clearance <30 mL/min
medical condition likely to cause death within 24 months
enrolled in a therapeutic vaccine or immunotherapy trial
enrolled in another trial investigating the impact of another intervention on HIV disease progression
HIV elite controller / long-term non-progressor

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00860977

Contacts

Contact: Sharon L Walmsley, MD FRCPC MSc	416-340-4800 ext 3871	sharon.walmsley@uhn.on.ca
Contact: Darrell HS Tan, MD FRCPC	416-340-4800 ext 2240	darrell.tan@gmail.com

Locations

Argentina
Fundación Huesped	Active, not recruiting
Buenos Aires, Argentina, C1202ABB
Brazil
Instituto de Pesquisa Clínica Evandro Chagas	Active, not recruiting
Rio de Janeiro, Brazil
Canada, Alberta
University of Alberta	Recruiting
Edmonton, Alberta, Canada, T6G 2C8
Contact: Barbara Romanowski, MD 780-436-4900
Principal Investigator: Barbara Romanowski, MD
Canada, British Columbia
Downtown ID Clinic	Recruiting
Vancouver, British Columbia, Canada, V6Z 2C7
Contact: Brian Conway, MD 604 642 6429
Principal Investigator: Brian Conway, MD
Cool Aid Community Health Centre	Recruiting
VIctoria, British Columbia, Canada, V8W 1M8
Contact: Chris Fraser, MD 250-385-1466
Principal Investigator: Chris Fraser, MD
Canada, Nova Scotia
CDHA, QEII Health Sciences Centre	Recruiting
Halifax, Nova Scotia, Canada, B3H 2Y9
Contact: David Haase, MD 902-473-7786
Principal Investigator: David Haase, MD
Canada, Ontario
McMaster University Health Sciences Centre	Recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: Fiona Smaill, MD 905-521-2100 ext. 76332
Principal Investigator: Fiona Smaill, MD
University of Ottawa Health Services	Recruiting
Ottawa, Ontario, Canada, K1N 6N5
Contact: Don Kilby, MD 613-654-3950
Principal Investigator: Don Kilby, MD
The Ottawa Hospital, General Campus Divsions of Infectious Diseases	Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Bill Cameron, MD 613-737-8902
Principal Investigator: Bill Cameron, MD
St. Michael's Hospital	Active, not recruiting
Toronto, Ontario, Canada, M5B 1W8
St. Clair Medical Associates	Recruiting
Toronto, Ontario, Canada, M4K 1N1
Contact: Ken Logue, MD 416- 966-0178
Principal Investigator: Ken Logue, MD
Sunnybrook Health Science Centre	Recruiting
Toronto, Ontario, Canada, M2N 3M5
Contact: Anita Rachlis, MD 416-480-4689
Principal Investigator: Anita Rachlis, MD
University Health Network	Recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Sharon L Walmsley, MD FRCPC 416-340-4800 ext 3871 sharon.walmsley@uhn.on.ca
Contact: Darrell HS Tan, MD FRCPC 416-340-4800 ext 2240
Sub-Investigator: Darrell HS Tan, MD FRCPC
Principal Investigator: Sharon L Walmsley, MD
Maple Leaf Medical Clinic	Recruiting
Toronto, Ontario, Canada, M5B 1L6
Contact: Jason Brunetta 416-465-0856
Principal Investigator: Jason Brunetta, MD
Windsor Regional Hospital	Recruiting
Windsor, Ontario, Canada, N8W 1E3
Contact: Jeffery Cohen, MD 519-254-6115
Principal Investigator: Jeffery Cohen, MD
Canada, Quebec
Montreal Chest Institute	Recruiting
Montreal, Quebec, Canada, H2X 2P4
Contact: Marina Klein, MD 514-843-2090
Principal Investigator: Marina Klein, MD
Centre Hospitalier de l'Université de Montréal	Recruiting
Montréal, Quebec, Canada, H2L 4M1
Contact: Claude Fortin, MD 514 890 8000 Ext 24723
Principal Investigator: Claude Fortin, MD
Clinique Médicale du Quartier Latin	Recruiting
Montréal, Quebec, Canada, H2L 5B1
Contact: Jean-Guy Baril, MD 514-285-2226
Principal Investigator: Jean-Guy Baril, MD
Canada
Centre Hospitalier Universitaire de Quebec-Pavillon CHUL	Recruiting
Quebec, Canada, G1V 4G2
Contact: Sylvie Trottier, MD 418-654-2705
Principal Investigator: Sylvie Trottier, MD

Sponsors and Collaborators

University Health Network, Toronto

Investigators

Principal Investigator:	Sharon L Walmsley, MD FRCPC MSc	University Health Network, Toronto
Principal Investigator:	Darrell HS Tan, MD FRCPC	University Health Network, Toronto

More Information

Additional Information:

CIHR Canadian HIV Trials Network homepage This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Dr Sharon Walmsley, Dr Darrell Tan, CIHR Canadian HIV Trials Network
ClinicalTrials.gov Identifier:	NCT00860977 History of Changes
Other Study ID Numbers:	CTN-240, ISRCTN66756285
Study First Received:	March 11, 2009
Last Updated:	December 22, 2010
Health Authority:	Canada: Health Canada

Keywords provided by University Health Network, Toronto:

HIV
Herpes simplex virus type 2
Genital herpes
Treatment Naive

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome
HIV Infections
Herpes Simplex
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

Herpesviridae Infections
DNA Virus Infections
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Valacyclovir
Acyclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012