Document 1098
 DOCN  M94A1098
 TI    Characterisation of HIV isolated from patients enrolled in the Alpha ddI
       Trial.
 DT    9412
 AU    Zheng NN; Simasathiansophan S; McQueen PW; Hurren L; Evans L; Delaney
       SF; Penny R; Cooper DA; Dept of Biotechnology, University of NSW,
       Kensington, Australia.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):21 (abstract no. 376A). Unique
       Identifier : AIDSLINE ICA10/94371477
 AB    OBJECTIVES: To establish whether: there is in vitro evidence of reduced
       ddI sensitivity of HIV in infected individuals receiving ddI; the
       emergence of resistance to ddI is associated with any change in
       sensitivity to ZDV; the emergence of SI virus and resistance to ddI
       correlate with clinical progression of the disease; there is a
       relationship between SI/NSI virus and resistance. METHODS: 175 people
       (ZDV intolerant) were recruited in the MRC/INSERM Alpha Trial to test
       the efficacy and safety of high-dose (750mg daily) or low-dose (200mg
       daily) ddI. Sensitivity of viral isolates to ZDV and ddI was determined.
       ZDV resistant mutation at codon 215 of the RT gene was detected by
       selective PCR. PCR products of the RT gene were sequenced. SI phenotype
       was determined using the MT-2 syncytia induction assay. RESULTS:
       Mutation at codon 215 was found in 48 patients; 22 also showing wild
       type 215. 287 samples were SI phenotyped. 59% of the 2 week samples
       showed NSI virus. After 12 weeks ddI therapy NSI phenotype increased to
       75%, declining again as therapy continued. Sequential data will be
       presented. In -2 wk isolates of 5 patients the virus was ZDV resistant
       and ddI sensitive. The sequential isolates of these 5 patients were ZDV
       and ddI resistant. Sequencing of these sequential isolates is underway.
       DISCUSSION AND CONCLUSIONS: Although all patients entering the trial
       were classified as ARC or AIDS, not all the isolates were SI. A high
       percentage of NSI isolates in week 12 samples suggests that ddI may be
       useful for partial containment of the expression of SI virus during the
       early stages of therapy. Although trends for individual patients varied,
       in general there was stability of ZDV sensitivity and an increase in ddI
       resistance with time.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY/MICROBIOLOGY
       AIDS-Related Complex/*DRUG THERAPY/MICROBIOLOGY  *Codon
       Didanosine/PHARMACOLOGY/*THERAPEUTIC USE  Human  HIV/DRUG
       EFFECTS/*ISOLATION & PURIF  Mutation  Polymerase Chain Reaction  Reverse
       Transcriptase/*GENETICS  Zidovudine/THERAPEUTIC USE  MEETING ABSTRACT

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