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

Study Overview
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Brief Summary
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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.

Official Title
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VALacyclovir In Delaying Antiretroviral Treatment Entry

Conditions
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HIV Infection, Herpes Simplex Type II, HIV Infections

Intervention / Treatment
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* Drug: valacyclovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily | Drug: Placebo<br>* Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily<br>|
| Experimental: Valacyclovir<br>oral valacyclovir 500mg twice daily | Drug: valacyclovir<br>* oral valacyclovir 500mg twice daily<br>* Other names: Valtrex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| annual rate of change in CD4 count, calculated as the slope of participants' CD4 count change / time. |  | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed acyclovir-resistant HSV |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Herpes simplex virus type II, Genital herpes, Treatment Naive