Document 0641
 DOCN  M94A0641
 TI    Novel mutations associated with HIV-1 resistance to AZT.
 DT    9412
 AU    Hooker DJ; Gurusinghe AD; Land SA; Birch CJ; McGavin C; Tachedjian G;
       Deacon NJ; AIDS Molecular Biology Lab, NCHVR Macfarlane Burnet Cent.
       for; Med. Res., Fairfield, Vic.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:63 (abstract no. TB4).
       Unique Identifier : AIDSLINE ASHM5/94349014
 AB    Associated with AZT therapy is the emergence in patients of drug
       resistant isolates of HIV-1. Certain mutations observed in the reverse
       transcriptase (RT) gene/protein upon AZT therapy, namely at codons 41,
       67, 70, 215 and 219, have previously been reported to contribute to AZT
       resistance. By PCR amplification of patient PBL DNA and direct
       sequencing of PCR products we have determined HIV-1 RT sequence of
       AZT-sensitive and resistant isolate pairs, and of a series of isolates
       taken from a single patient before, during and after AZT therapy. In
       resistant isolates from pairs, mutations were seen at 41 and 215 but not
       67, 70 or 219. In the sequential series mutations Glu44 to Asp and
       Thr369 to lle correlated with drug therapy, as did previously reported
       mutations at 41, 67, 70 and 215 but not 219. However one additional
       mutation was observed in resistant isolates from all patients studied
       here, namely Leu210 to Trp. Due to the consistent association of Trp210
       with AZT resistance, we investigated its contribution by mutagenesis:
       compared to wild-type HXB2, HXB2 mutated to Trp210 generated virus which
       by IC50 was 3 fold more sensitive to AZT. Considering Trp210 has been
       observed only with other mutations in these patients, we are now
       examining its effect in conjunction with known resistance inducing
       mutations.
 DE    Codon/GENETICS  Drug Resistance, Microbial/GENETICS  Human  HIV
       Infections/MICROBIOLOGY  HIV-1/*DRUG EFFECTS/GENETICS
       Mutation/*GENETICS  Polymerase Chain Reaction  Reverse
       Transcriptase/ANTAGONISTS & INHIB/*GENETICS  Zidovudine/*PHARMACOLOGY
       MEETING ABSTRACT

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