Document 0642
 DOCN  M94A0642
 TI    In vitro generation and characterisation of foscarnet-resistant HIV-1.
 DT    9412
 AU    Tachedjian G; Mills J; Birch C; Macfarlane Burnet Centre, Fairfield
       Hospital, Australia.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:63 (abstract no. TB3).
       Unique Identifier : AIDSLINE ASHM5/94349013
 AB    Foscarnet (phosphonoformic acid) is a pyrophosphate analogue used for
       the treatment of CMV retinitis and acyclovir-resistant herpes simplex
       infections in AIDS patients. Foscarnet is also an inhibitor of HIV, and
       therefore long-term administration in patients may result in the
       emergence of foscarnet-resistant (Fos-R) virus. To investigate the
       potential of FosR HIV to emerge in vivo we have generated a resistant
       variant by in vitro selection in MT-2 cells using a clinical isolate.
       This strain was biologically cloned and compared to wild-type with
       respect to zidovudine, ddC, ddl and TIBO sensitivity. In addition, the
       sensitivity of the reverse transcriptase (RT) from this mutant to
       foscarnet, zidovudine and TIBO was analysed. Following 6 passages in
       increasing foscarnet concentrations, a resistant virus was selected with
       a 4-fold decrease in sensitivity to foscarnet at the IC50 level.
       Compared to the foscarnet-sensitive virus, the FosR variant was
       hypersensitive to TIBO and zidovudine while showing identical
       sensitivity profiles to ddC and ddl as determined in MT-2 cells.
       Resistance to foscarnet and hypersensitivity to TIBO were confirmed at
       the RT level while no consistent pattern was observed in the presence of
       AZTTP. Given the rapid emergence of FosR HIV, the possibility exists
       that such a variant may emerge in vivo.
 DE    Gene Products, gag/ANTAGONISTS & INHIB  Human  HIV Protease
       Inhibitors/*PHARMACOLOGY  HIV-1/*DRUG EFFECTS  HIV-2/*DRUG EFFECTS  In
       Vitro  Protein Precursors/ANTAGONISTS & INHIB  Virus Replication/*DRUG
       EFFECTS  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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