Document 0690
 DOCN  M94A0690
 TI    ZDV and ddI resistance in HIV isolated from patients enrolled in the
       alpha ddI trial.
 DT    9412
 AU    Zheng N; McQueen PW; Hurren L; Imrie A; Evans L; Delaney SF; Penny R;
       Cooper DA; Centre for Immunology, St. Vincents Hospital, Sydney.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:36 (abstract no. SC5).
       Unique Identifier : AIDSLINE ASHM5/94348965
 AB    Progressive HIV disease continues to occur despite the therapeutic use
       of antiviral agents such as didanosine (ddI) a azidothymidine (ZDV) in
       the management of HIV infection. The means by which HIV-1 is able to
       overcome these chemotherapeutic challenges remains unclear at this time.
       It seems unlikely that a single change in the virus could modify the
       disease process so profoundly. Several mechanisms have been proposed,
       such as the development of mutations conferring resistance to
       chemotherapy, the appearance of a more virulent virus variant, and the
       appearance of virus variants with different pathogenetic prognoses. Few
       opportunities, however, have arisen to evaluate the relative merits of
       such proposals in a suitably large, controlled and longitudinally
       followed population of individuals in receipt of antiviral treatment.
       The MRC/INSERM Alpha Trial was a randomised, double blind trial of the
       efficacy and safety of high-dose (HD; 750 mg daily) ddI versus low-dose
       (LD; 200 mg daily) ddI in humans infected with HIV-1 who were intolerant
       to ZDV. This multi-centre, multinational study commenced in 1990. At St.
       Vincents Hospital, Sydney 175 participants were recruited. This paper
       reports on the preliminary results which we have obtained from enrolled
       individuals at week -2 (pre ddI treatment), 24, 48 and 72. The presence
       of HIV-1 DNA with a ZDV mutation at codon 215 of the reverse
       transcriptase coding region has been found in 44 out of a total of 63
       patients tested prior to treatment. The remaining 19 only showed
       hybridisation for wild type codon 215. Results obtained for a ddI
       mutation at codon 74 of the reverse transcriptase will be presented, as
       well as an investigation of ZDV and ddI resistance using a drug
       susceptibility assay.
 DE    Comparative Study  Didanosine/*THERAPEUTIC USE  Dose-Response
       Relationship, Drug  Double-Blind Method  Drug Administration Schedule
       Drug Resistance/GENETICS  Human  HIV Infections/*DRUG
       THERAPY/MICROBIOLOGY  HIV-1/*DRUG EFFECTS/GENETICS  Mutation  Reverse
       Transcriptase/ANTAGONISTS & INHIB/GENETICS  Zidovudine/*THERAPEUTIC USE
       CLINICAL TRIAL  MEETING ABSTRACT  MULTICENTER STUDY  RANDOMIZED
       CONTROLLED TRIAL

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