Comparison of Brovavir Versus Acyclovir in the Treatment of Herpes in HIV-Infected Patients

Evaluation of Brovavir ( BV-ara-U; SQ 32,756 ) Versus Acyclovir in the Treatment of Localized Herpes Zoster in HIV-Infected Patients

To compare the efficacy of oral sorivudine (brovavir) and oral acyclovir for the treatment of localized herpes zoster in HIV-infected patients.

HIV-infected patients are at high risk for herpesvirus infections, including varicella-zoster virus ( VZV ) infections, also called shingles. Acyclovir, an approved drug, is widely used to treat VZV infections in the HIV population. Since no data from controlled studies are available to define the role of antiviral therapy for VZV infections in HIV-infected patients, a study is needed to test the relative efficacy of brovavir, an experimental antiviral drug, versus that of acyclovir.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Chickenpox
• Intervention / Treatment: Drug: Acyclovir; Drug: Sorivudine

Detailed Description

HIV-infected patients are at high risk for herpesvirus infections, including varicella-zoster virus ( VZV ) infections, also called shingles. Acyclovir, an approved drug, is widely used to treat VZV infections in the HIV population. Since no data from controlled studies are available to define the role of antiviral therapy for VZV infections in HIV-infected patients, a study is needed to test the relative efficacy of brovavir, an experimental antiviral drug, versus that of acyclovir.

One hundred-eighty patients are randomized to receive either brovavir or acyclovir as follows: brovavir or its matching placebo once daily and acyclovir or its matching placebo five times daily. Treatment continues for 10 days. Entry into the study must occur within 72 hours of lesion development. Patients are followed in person daily or at regular intervals during study drug administration and on days 14, 21, and 28, and then monthly by telephone for 11 months thereafter.

• Study Type: Interventional
• Enrollment: 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 900331079
      • Univ of Southern California / LA County USC Med Ctr
    • Los Angeles, California, United States, 90095
      • UCLA Med Ctr
    • Martinez, California, United States, 94553
      • Veterans Administration Med Ctr
    • Oakland, California, United States, 94609
      • Infectious Disease Med Group
    • San Diego, California, United States, 92134
      • San Diego Naval Hosp
    • San Francisco, California, United States, 94115
      • Mount Zion Med Ctr
  • Colorado
    • Denver, Colorado, United States, 80262
      • Univ of Colorado Health Sciences Ctr
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington Univ Med Ctr
    • Washington, District of Columbia, United States, 20422
      • Veterans Administration Med Ctr / Community AIDS Program
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Med College of Georgia
  • Hawaii
    • Honolulu, Hawaii, United States, 96816
      • Univ of Hawaii / Leahi Hosp
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush Presbyterian - Saint Luke's Med Ctr
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Hosp
    • Bethesda, Maryland, United States, 20892
      • Natl Institutes of Health / NIAID
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hosp
    • Boston, Massachusetts, United States, 02215
      • New England Deaconess Hosp
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Hosp
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Gen Hosp / Harvard Med School
  • Missouri
    • St Louis, Missouri, United States, 63108
      • Washington Univ
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Univ of New Mexico
  • New York
    • New York, New York, United States, 10003
      • Beth Israel Med Ctr
    • New York, New York, United States, 10021
      • Mem Sloan - Kettering Cancer Ctr
    • New York, New York, United States, 10025
      • Saint Luke's - Roosevelt Hosp Ctr
    • New York, New York, United States, 10029
      • Mount Sinai Med Ctr
    • Stony Brook, New York, United States, 11794
      • SUNY / Health Sciences Ctr at Stony Brook
    • Syracuse, New York, United States, 13210
      • SUNY / Health Sciences Ctr at Syracuse
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Med Ctr
  • Ohio
    • Cincinnati, Ohio, United States, 452670523
      • Univ Dermatology Associates
    • Columbus, Ohio, United States, 43210
      • Ohio State Univ / ACTU-Univ Clinic
    • Dayton, Ohio, United States, 45428
      • Dayton Veterans Administration Med Ctr
    • Toledo, Ohio, United States, 43699
      • Med College of Ohio
  • Oregon
    • Portland, Oregon, United States, 972109951
      • Portland Veterans Adm Med Ctr / Rsch & Education Grp
  • Texas
    • Dallas, Texas, United States, 75390
      • Univ of Texas, Southwestern Med Ctr of Dallas
    • Dallas, Texas, United States, 75216
      • Dallas Veterans Administration Med Ctr
    • Galveston, Texas, United States, 775550882
      • Univ TX Galveston Med Branch
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 782847881
      • Univ TX San Antonio Health Science Ctr
    • Temple, Texas, United States, 76508
      • Scott and White Hosp
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Univ of Virginia Health Sciences Ctr
    • Norfolk, Virginia, United States, 23507
      • Virginia Clinical Research Inc
    • Salem, Virginia, United States, 24153
      • Salem Veterans Administration Med Ctr
  • Washington
    • Seattle, Washington, United States, 98104
      • Univ of Washington
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53213
      • Great Lakes Hemophilia Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Medication for concurrent conditions (e.g., insulin, antihypertensives, bronchodilators, digoxin) or antibacterials or antifungals to treat concurrent infections at other sites or superinfection of the zoster lesion.
• Anti-inflammatory, analgesic (including narcotic analgesic), or antipyretic agents.
• Antidepressants and antipsychotics such as amitriptyline and/or fluphenazine.
• Nerve blocks.
• AZT, ddI, ddC, and amantadine.
• Low-dose corticosteroids for treatment of an underlying (not zoster-related) disease.
• Immune modulators without varicella-zoster virus activity (e.g., GM-CSF, gp160 vaccine).

Patients must have:

• HIV infection.
• Localized, cutaneous herpes zoster (shingles).
• Zoster-associated rash present for 3 or fewer days prior to entry.

Prior Medication:

Allowed:

• Zidovudine.
• ddI.
• ddC.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions and symptoms are excluded:

• Chickenpox.
• Evidence of visceral dissemination (organ involvement, i.e., brain, liver, or lung) and/or cutaneous dissemination (more than 20 vesicles in dermatomes beyond contiguous dermatomes) of zoster.
• Zoster-like lesion caused by organism other than VZV (e.g., HSV, enterovirus, or Mycoplasma).
• Bacterial superinfection of zoster lesion.
• Zosteriform lesion previously treated with topical antiviral agents.
• Acute, life-threatening opportunistic infection requiring treatment (ongoing suppressive or prophylactic maintenance therapy other than ganciclovir or foscarnet is permitted).
• Concurrent severe disease that may either impair ability to take oral medication in capsule or tablet form or limit survival during the 10-day treatment period or during acute phase follow-up (28 days).
• Suspected acute deterioration of renal or hepatic function.
• Mental impairment that precludes ability to comply with protocol.
• Any condition that would render the patient unsuitable for treatment.

Concurrent Medication:

Excluded during acute phase of study:

• Antiviral medications other than AZT, ddI, ddC, or anti-Parkinson's drugs (i.e., amantadine).
• Interferon.
• Isoprinosine.
• Levamisole.
• Transfer factor.
• Topical virucidal agents, oxidizing agents, DMSO, cell division-stimulating/healing agents, or astringents.
• Topical anesthetics (such as capsaicin or xylocaine).
• Topical creams or ointments that may interfere with evaluation of zoster lesions.
• Cimetidine.
• Fluorouracil or its derivatives, flucytosine, or cyclophosphamide (during drug administration and for 2 weeks thereafter).
• High-dose corticosteroids.
• Anticoagulant therapy (heparin locks and low-dose warfarin sodium permitted).
• Probenecid or derivatives.
• Treatment for any acute, life-threatening opportunistic infection (suppressive or prophylactic maintenance therapy other than ganciclovir or foscarnet is permitted).

Use of the following drugs is discouraged during the long-term phase of the study:

• Antiviral agents with VZV activity.
• Immunomodulators with presumed VZV activity.
• VZV immune globulin.
• Capsaicin.
• Cimetidine.

Patients with the following prior conditions are excluded:

• History of immediate hypersensitivity or serum sickness reaction or idiosyncratic reaction (such as hepatic necrosis or Stevens-Johnson syndrome) to any nucleoside analog antiviral agent or to any anticancer therapy with cytolytic agents.

Prior Medication:

Excluded within 1 month prior to entry:

• Any investigational drugs or treatments not licensed for any indication (other than ddI or ddC).

Excluded within 2 weeks prior to entry:

• Any systemic antiviral therapy, including ganciclovir, foscarnet, vidarabine, acyclovir, or ribavirin.
• Any antiretroviral drug other than zidovudine, ddI, and ddC.
• Immune globulin (e.g., IgG, VZIG).

Excluded within 72 hours prior to entry:

• Cyclophosphamide.
• Flucytosine.
• Fluorouracil or its derivatives.

Alcohol or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; Glaxo Wellcome
• Investigators: Study Chair: Crumpacker C

Publications and helpful links

General Publications

• Gnann J, et al. Sorivudine (BV-araU) versus acyclovir for Herpes zoster in HIV-infected patients. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:55

Study record dates

Study Major Dates

• Primary Completion (Actual): September 1, 1996

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): March 1, 2011
• Last Update Submitted That Met QC Criteria: February 25, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Antiviral Agents; Herpes Zoster; Acyclovir; sorivudine
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Chickenpox; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Acyclovir; Sorivudine
• Other Study ID Numbers: ACTG 169; Protocol -38/-022