       Document 0657
 DOCN  M9620657
 TI    Emergence and clinical relevance of mutations associated with zidovudine
       resistance in asymptomatic HIV-1 infected patients.
 DT    9602
 AU    Calderon EJ; Torres Y; Medrano FJ; Luque F; Larder B; Rey C;
       Sanchez-Quijano A; Lissen E; Leal M; Department of Internal Medicine,
       Virgen del Rocio University; Hospital, Seville, Spain.
 SO    Eur J Clin Microbiol Infect Dis. 1995 Jun;14(6):512-9. Unique Identifier
       : AIDSLINE MED/96082795
 AB    The dynamics leading to the emergence of a zidovudine-resistant mutation
       at codon 215 of the reverse transcriptase coding region was investigated
       in a cohort of HIV-infected individuals who received early zidovudine
       therapy. Clinical implications and the role of the resistance mutation
       at codon 41 were also assessed. Thirty-eight initially asymptomatic
       HIV-infected patients with a CD4+ cell count above 400 cells/mm3 were
       followed for a mean period of 121 weeks (20 received zidovudine and 18
       matching placebo). Specific mutations in the HIV-1 reverse transcriptase
       coding region conferring resistance to zidovudine were detected using a
       selective polymerase chain reaction. During the follow-up period a
       mutation at codon 215 was detected in eight (40%) of the individuals in
       the zidovudine group, and in two of these eight subjects, a mutation at
       codon 41 was found. During the study, disease progression occurred in
       seven of the eight (88%) patients with a mutation at codon 215, compared
       with 7 of 18 (39%) patients assigned to the placebo group and 3 of the
       12 (25%) patients receiving zidovudine treatment who did not develop a
       215-mutant strain (p < 0.05). At entry, none of the patients harbored
       MT-2 tropic virus. Therefore, the emergence of a zidovudine-resistant
       mutation at codon 215 is associated with subsequent disease progression
       in asymptomatic HIV-infected patients who receive zidovudine
       monotherapy. This association suggests that the mutation at codon 215 is
       involved in a loss of therapeutic efficacy and, therefore, patients
       should be monitored during treatment with zidovudine.
 DE    Adult  Antiviral Agents/*THERAPEUTIC USE  Base Sequence  Codon  Cohort
       Studies  CD4 Lymphocyte Count  Disease Progression  Double-Blind Method
       Drug Resistance, Microbial/GENETICS  Female  Human  HIV
       Seropositivity/*DRUG THERAPY/IMMUNOLOGY  HIV-1/*DRUG EFFECTS/GENETICS
       Male  Molecular Sequence Data  *Mutation  Polymerase Chain Reaction
       RNA-Directed DNA Polymerase  Support, Non-U.S. Gov't
       Zidovudine/*THERAPEUTIC USE  CLINICAL TRIAL  JOURNAL ARTICLE  RANDOMIZED
       CONTROLLED TRIAL

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

