       Document 0768
 DOCN  M9640768
 TI    Herpes simplex virus resistance to acyclovir: clinical relevance.
 DT    9604
 AU    Pottage JC Jr; Kessler HA; Department of Medicine, Rush Medical College,
       Chicago, Illinois,; USA.
 SO    Infect Agents Dis. 1995 Sep;4(3):115-24. Unique Identifier : AIDSLINE
       MED/96034253
 AB    Herpes simplex virus (HSV) infections are very common in the general
       population and can be treated with the nucleoside analogue acyclovir.
       Acyclovir is initially phosphorylated intracellularly in HSV-infected
       cells by a viral-specific thymidine kinase to acyclovir-monophosphate.
       The monophosphate is subsequently di- and triphosphorylated by host
       cellular kinases to the active form of the drug, which inhibits HSV DNA
       polymerase and incorporates into the elongating viral DNA and causes
       chain termination. Acyclovir resistance has been increasingly described
       and is caused by mutations in either the thymidine kinase or the DNA
       polymerase genes. These mutations result in decreased or absent HSV
       thymidine kinase production, altered affinity of the thymidine kinase
       for acyclovir-triphosphate, or altered affinity of the HSV DNA
       polymerase for acyclovir-triphosphate. Thymidine kinase deficiency
       accounts for approximately 95% of acyclovir-resistant isolates. Clinical
       disease due to acyclovir-resistant HSV occurs primarily in
       immunocompromised patients and is usually characterized by a chronic,
       progressive ulcerative mucocutaneous disease with prolonged shedding of
       virus. Several large surveys have been done in an effort to determine
       the incidence of in vitro and clinical acyclovir resistance. Among
       immunocompetent hosts, even those who have received > or = 6 years of
       continuous acyclovir, the prevalence of acyclovir-resistant isolates has
       remained stable at approximately 3%. Only three cases of clinical
       resistance of HSV to acyclovir have been reported. However, the
       incidence in immunocompromised patients, particularly those with AIDS
       and those who have had bone marrow transplants, is increasing.
       Transmission of acyclovir-resistant isolates from person to person has
       not been documented, but due to the increased use of acyclovir and newer
       drugs, such as famciclovir, there is great concern that this
       transmission might occur in the future. Continued surveillance in both
       immunocompetent and immunocompromised hosts for the development of
       clinical acyclovir-resistant HSV disease is necessary.
 DE    Acyclovir/PHARMACOLOGY/*THERAPEUTIC USE  Antiviral
       Agents/PHARMACOLOGY/*THERAPEUTIC USE  AIDS-Related Opportunistic
       Infections/DRUG THERAPY  Drug Resistance, Microbial  Herpes
       Simplex/*DRUG THERAPY/EPIDEMIOLOGY/PATHOLOGY  Herpesvirus 1, Human/*DRUG
       EFFECTS  Herpesvirus 2, Human/*DRUG EFFECTS  Human  Immunocompromised
       Host  United States/EPIDEMIOLOGY  JOURNAL ARTICLE  REVIEW  REVIEW,
       TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

