Document 0035
 DOCN  M95B0035
 TI    Potential mechanism for sustained antiretroviral efficacy of AZT-3TC
       combination therapy.
 DT    9511
 AU    Larder BA; Kemp SD; Harrigan PR; Antiviral Therapeutic Research Unit,
       Wellcome Research; Laboratories, Beckenham, Kent, UK.
 SO    Science. 1995 Aug 4;269(5224):696-9. Unique Identifier : AIDSLINE
       MED/95350663
 AB    Combinations of antiretroviral drugs that prevent or delay the
       appearance of drug-resistant human immunodeficiency virus-type 1 (HIV-1)
       mutants are urgently required. Mutants resistant to 3'-azidothymidine
       (AZT, zidovudine) became phenotypically sensitive in vitro by mutation
       of residue 184 of viral reverse transcriptase to valine, which also
       induced resistance to (-)2'-deoxy-3'-thiacytidine (3TC). Furthermore,
       AZT-3TC coresistance was not observed during extensive in vitro
       selection with both drugs. In vivo AZT-3TC combination therapy resulted
       in a markedly greater decreased in serum HIV-1 RNA concentrations than
       treatment with AZT alone, even though valine-184 mutants rapidly
       emerged. Most samples assessed from the combination group remained AZT
       sensitive at 24 weeks of therapy, consistent with in vitro mutation
       studies.
 DE    Antiviral Agents/*PHARMACOLOGY/THERAPEUTIC USE  Base Sequence  Cell Line
       Codon  CD4 Lymphocyte Count  Drug Resistance, Microbial  Drug Therapy,
       Combination  Hela Cells  Human  HIV Infections/*DRUG THERAPY/VIROLOGY
       HIV-1/*DRUG EFFECTS/ENZYMOLOGY/GROWTH & DEVELOPMENT/GENETICS  Molecular
       Sequence Data  Mutagenesis, Site-Directed  Point Mutation  Reverse
       Transcriptase/*ANTAGONISTS & INHIB/GENETICS  RNA, Viral/BLOOD  Serial
       Passage  Zalcitabine/*ANALOGS & DERIVATIVES/PHARMACOLOGY/THERAPEUTIC USE
       Zidovudine/*PHARMACOLOGY/THERAPEUTIC USE  CLINICAL TRIAL  CLINICAL
       TRIAL, PHASE II  CLINICAL TRIAL, PHASE III  JOURNAL ARTICLE  RANDOMIZED
       CONTROLLED TRIAL

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