home
***
CD-ROM
|
disk
|
FTP
|
other
***
search
/
Software Vault: The Sapphire Collection
/
Software Vault (Sapphire Collection) (Digital Impact).ISO
/
cdr16
/
med9410d.zip
/
M94A0642.TXT
< prev
next >
Wrap
Text File
|
1994-10-21
|
2KB
|
37 lines
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
protected by Copyright Law (Title 17, U.S.Code).