Acyclovir-Resistant Varicella Zoster Virus Infection after Chronic Oral Acyclovir Therapy in Patients with the Acquired Immunodeficiency Syndrome (AIDS)

  1. Mark A. Jacobson, MD;
  2. Timothy G. Berger, MD;
  3. Senih Fikrig, MD;
  4. Paul Becherer, MD;
  5. John W. Moohr, MD;
  6. Sylvia C. Stanat, BA; and
  7. Karen K. Biron, PhD

    Abstract

    Four patients with human immunodeficiency virus (HIV) infection who received chronic oral acyclovir therapy for suppression of recurrent varicella zoster or herpes simplex virus infection developed persistent disseminated hyperkeratotic papules that failed to heal with intravenous or highdose oral acyclovir therapy. Varicella zoster virus, resistant to acyclovir in vitro, was isolated from skin lesions of all four patients. Three patients were adults in whom the acquired immunodeficiency syndrome (AIDS) had been diagnosed 12 to 20 months before isolation of acyclovir-resistant varicella zoster virus. The fourth patient was a perinatally HIV-infected child who developed primary varicella infection at age 7 years when profoundly immunosuppressed (absolute CD4+ lymphocyte count < 50 cells/ μL). Mean antiviral susceptibilities (ED50 values) of the four clinical isolates compared with the ED50 values of the reference strain Oka were 85 compared with 3.3 ¼mol/L for acyclovir, 1.4 compared with 0.8 ¼mol/L for vidarabine, and 123 compared with 117 ¼mol/L for foscarnet. When assayed by [125I]-dC plaque autoradiography, 90% to 100% of the viral isolate populations had altered or no measurable thymidine kinase function. Acyclovir-resistant varicella zoster virus infection may complicate long-term oral acyclovir administration in patients with AIDS and may be associated with the appearance of atypical hyperkeratotic papules.

    Article and Author Information

    • From University of California and San Francisco General Hospital, San Francisco, California; State University of New York, Health Sciences Center at Brooklyn, Brooklyn, New York; University of North Carolina, Chapel Hill, North Carolina; and Burroughs Wellcome Company, Research Triangle Park, North Carolina. For current author addresses, see end of text.

    • Requests for Reprints: Karen K. Biron, PhD, Division of Virology, Burroughs Wellcome Company, 3030 Cornwallis Road, Research Triangle Park, NC 27709.

    • Current Author Addresses: Dr. Jacobson: Ward 84, Bldg 80, San Francisco General Hospital, 995 Potrero, San Francisco, CA 94110. Dr. Berger: Room 4M70, San Francisco General Hospital, 1001 Potrero, San Francisco, CA 94110.

      Dr. Fikrig: SUNY Health Science Center at Brooklyn, 450 Clarkson Ave., Box 49, Brooklyn, NY 11203.

      Dr. Moohr: Woodhull Medical and Mental Center, Dept. of Pediatrics, 760 Broadway, Brooklyn, NY 11206.

      Dr. Becherer: University of North Carolina School of Medicine, Division of Infectious Diseases, CB# 7030, 547 Burnett-Womack, Chapel Hill, NC 27599-7030.

      Ms. Stanat and Dr. Biron: Burroughs Wellcome Company, Division of Virology, 3030 Cornwallis Road, Research Triangle Park, NC 27709.

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    1. Ann Intern Med February 1, 1990 vol. 112 no. 3 187-191
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