Document 0599
 DOCN  M9550599
 TI    Sanctuary growth of human immunodeficiency virus in the presence of
       3'-azido-3'-deoxythymidine.
 DT    9505
 AU    Medina DJ; Tung PP; Lerner-Tung MB; Nelson CJ; Mellors JW; Strair RK;
       Cancer Institute of New Jersey, Robert Wood Johnson School of; Medicine,
       University of Medicine and Dentistry of New Jersey,; Piscataway 08854.
 SO    J Virol. 1995 Mar;69(3):1606-11. Unique Identifier : AIDSLINE
       MED/95156587
 AB    Human immunodeficiency virus (HIV) resistance to the nonnucleoside
       reverse transcriptase inhibitors emerges very rapidly under selection in
       culture and in patients. In contrast, zidovudine
       (3'-azido-3'-deoxythymidine [AZT])-resistant HIV generally emerges in
       patients only after more-prolonged therapy. Although HIV can be cultured
       from many patients shortly after the initiation of AZT treatment,
       characterization of the virus that is cultured generally indicates that
       it is sensitive to AZT. To initiate an evaluation of the mechanisms
       contributing to early HIV breakthrough in the presence of AZT and other
       nucleoside analogs, we have utilized replication-defective HIV encoding
       reporter genes. These recombinant HIV allow a quantitative analysis of a
       single cycle of infection. Results with these defective HIV indicate
       that early infection in the presence of AZT often results from the
       infection of a cell which is refractory to the antiretroviral effects of
       AZT. Characterization of a cell line derived from one such cell has
       demonstrated decreased accumulation of AZT triphosphate, increased
       phosphorylation of thymidine to thymidine triphosphate, and increased
       levels of thymidine kinase activity. In addition, AZT inhibition of
       replication-competent HIV infection is also significantly impaired in
       this cell line. Attempts to detect and characterize the mechanisms
       responsible for early viral infection after initiation of AZT therapy
       may result in the development of new strategies for prolonged
       suppression of viral infection prior to the emergence of drug-resistant
       virus.
 DE    Cell Line  Dose-Response Relationship, Drug  Drug Resistance  Human
       HIV-1/*DRUG EFFECTS/GROWTH & DEVELOPMENT  In Vitro  Phosphorylation
       Support, Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.  Support, U.S.
       Gov't, P.H.S.  Thymidine/METABOLISM  Virus Replication/*DRUG EFFECTS
       Zidovudine/*PHARMACOLOGY/TOXICITY  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).