Document 0692
 DOCN  M9440692
 TI    Resistance to AZT and ddC during long-term combination therapy in
       patients with advanced infection with human immunodeficiency virus.
 DT    9404
 AU    Richman DD; Meng TC; Spector SA; Fischl MA; Resnick L; Lai S; Department
       of Pathology, University of California, San Diego, La; Jolla 92093-0679.
 SO    J Acquir Immune Defic Syndr. 1994 Feb;7(2):135-8. Unique Identifier :
       AIDSLINE MED/94133082
 AB    To ascertain whether combination therapy with zidovudine (AZT) and
       zalcitabine (ddC) delayed the emergence of AZT resistance, isolates of
       human immunodeficiency virus (HIV) were evaluated from 15 previously
       untreated patients with advanced HIV disease who received combination
       therapy. Eighteen sequential viral isolates were available from 15
       patients who received > or = 6 months of combination therapy. Isolates
       from eight (73%) of 11 patients obtained between 24 and 48 weeks of
       therapy were AZT resistant [50% inhibitory concentration (IC50) > or =
       0.45 microM; range, 0.45-2.0 microM]. Four of these eight patients
       yielded virus isolates that were highly AZT resistant (IC50 > 1.0
       microM). No changes in ddC susceptibility were discerned. The median
       IC50 for ddC was 0.2 microM and ranged from 0.07 to 0.5 microM. The CD4
       cell counts of patients with AZT-sensitive virus tended to have higher
       median areas under the curve (AUC) and greater increases compared with
       patients who had AZT-resistant virus. They also had higher means and
       ranges of the average CD4 cell counts at week 36 (p = 0.01) and week 48
       (p = 0.04). These data would indicate that the previously described more
       sustained CD4 cell responses conferred by the addition of ddC to AZT
       therapy cannot be ascribed to delayed emergence of AZT resistance with
       combination therapy.
 DE    Drug Resistance, Microbial  Drug Therapy, Combination  Hela Cells  Human
       HIV/*DRUG EFFECTS  HIV Infections/*DRUG THERAPY  Leukocyte Count
       Support, U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.  Time
       Factors  T4 Lymphocytes/CYTOLOGY  Zalcitabine/*PHARMACOLOGY/THERAPEUTIC
       USE  Zidovudine/*PHARMACOLOGY/THERAPEUTIC USE  CLINICAL TRIAL  JOURNAL
       ARTICLE

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