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

Condition(s) targeted: HIV Infection; Herpesvirus 2, Human; HIV Infections

Intervention: valacyclovir (Drug); Placebo (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Canadian HIV Trials Network

Official(s) and/or principal investigator(s):
Sharon L Walmsley, MD FRCPC MSc, Principal Investigator, Affiliation: University Health Network, Toronto
Darrell HS Tan, MD FRCPC, Principal Investigator, Affiliation: University Health Network, Toronto

Overall contact:
Sharon L Walmsley, MD FRCPC MSc, Phone: 416-340-4800, Ext: 3871, Email: sharon.walmsley@uhn.on.ca

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.

Official title: VALacyclovir In Delaying Antiretroviral Treatment Entry

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Primary outcome: 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.

Secondary outcome:

Annual rate of change in CD4 count, calculated as the slope of patients' CD4 count change / time

Annual rate of change in the CD4 cell count percentage, calculated as the slope of the patient's CD4 count percentage change over time

Log10 plasma HIV viral load

Treatment-emergent adverse events and laboratory abnormalities

Frequency of episodes of HSV reactivations at any anatomic site

Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed acyclovir-resistant HSV

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- adults aged over 18 years

- documented HIV-1 infection

- documented HSV-2 seropositivity

- maximum 2 episodes recurrent symptomatic HSV recurrences per year

- neither currently using nor 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:

- pregnant

- receiving chemotherapy or chronic steroid therapy

- estimated creatinine clearance <30 mL/min

- active opportunistic infection

- 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

Sharon L Walmsley, MD FRCPC MSc, Phone: 416-340-4800, Ext: 3871, Email: sharon.walmsley@uhn.on.ca

Instituto de Pesquisa Clínica Evandro Chagas, Rio de Janeiro, Brazil

University Health Network, Toronto, Ontario M5G 2N2, Canada

CIHR Canadian HIV Trials Network homepage

Starting date: September 2009
Ending date: August 2014
Last updated: April 6, 2009