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M94A0690.TXT
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1994-10-21
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).