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.

Condition	Treatment or Intervention	Phase
HIV Infections Chickenpox	Drug: Sorivudine  Drug: Acyclovir	Phase II

Further Study Details: 

Expected Total Enrollment:  180

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

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

Study chairs or principal investigators

Crumpacker C,  Study Chair

Study ID Numbers:  ACTG 169; Protocol -38/-022
Record last reviewed:  January 2003
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000953
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08