Document 0470
 DOCN  M9550470
 TI    Zidovudine resistance and HIV-1 disease progression during
       antiretroviral therapy. AIDS Clinical Trials Group Protocol 116B/117
       Team and the Virology Committee Resistance Working Group.
 DT    9505
 AU    D'Aquila RT; Johnson VA; Welles SL; Japour AJ; Kuritzkes DR; DeGruttola
       V; Reichelderfer PS; Coombs RW; Crumpacker CS; Kahn JO; et al;
       Massachusetts General Hospital, Beth Israel Hospital, Harvard; Medical
       School, Boston.
 SO    Ann Intern Med. 1995 Mar 15;122(6):401-8. Unique Identifier : AIDSLINE
       MED/95160383
 AB    OBJECTIVE: To evaluate the association between resistance of human
       immunodeficiency virus type 1 (HIV-1) to zidovudine and clinical
       progression. DESIGN: Retrospective analysis of specimens from patients
       in the AIDS Clinical Trials Group (ACTG) protocol 116B/117, a randomized
       comparison of didanosine with continued zidovudine therapy in patients
       with advanced HIV-1 disease who had received 16 weeks or more of
       previous zidovudine therapy. SETTING: Participating ACTG virology
       laboratories. PATIENTS: 187 patients with baseline HIV-1 isolates.
       MEASUREMENTS: Zidovudine susceptibility testing and assays for
       syncytium-inducing phenotype were done on baseline HIV-1 isolates.
       Relative hazards for clinical progression or death associated with
       baseline clinical, virologic, and immunologic factors were determined
       from Cox proportional hazards regression models. RESULTS: Compared with
       other patients, 15% (26 of 170) with isolates showing high-level
       zidovudine resistance (50% inhibitory zidovudine concentration > or =
       1.0 microM) had 1.74 times the risk for progressing to a new
       AIDS-defining event or death (95% CI, 1.00 to 3.03) and 2.78 times the
       risk for death (CI, 1.21 to 6.39) in analyses that controlled for
       baseline CD4+ T-lymphocyte count, syncytium-inducing HIV-1 phenotype,
       disease stage, and randomized treatment assignment. The clinical benefit
       of didanosine was not limited to patients with highly
       zidovudine-resistant baseline HIV-1 isolates. CONCLUSIONS: High-level
       resistance of HIV-1 to zidovudine predicted more rapid clinical
       progression and death when adjusted for other factors. However, patients
       with advanced HIV-1 disease may benefit from a change in monotherapy
       from zidovudine to didanosine whether high-level HIV-1 resistance to
       zidovudine is present or absent, and laboratory assessment of zidovudine
       resistance is not necessary for deciding when to switch monotherapy from
       zidovudine to didanosine.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY/IMMUNOLOGY/  VIROLOGY
       Adult  CD4 Lymphocyte Count  Didanosine/THERAPEUTIC USE  Drug
       Resistance, Microbial  Drug Therapy, Combination  Female  Human
       HIV-1/*DRUG EFFECTS  Male  Prognosis  Proportional Hazards Models
       Retrospective Studies  Risk Factors  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.
       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).