3rd International Workshop on HIV Drug Resistance 2-5 August 1994, Kauai, Hawaii, USA

CHARACTERISATION OF HIV ISOLATED FROM PATIENTS ENROLLED IN THE ALPHA ddI TRIAL

Int Wkshop HIV Drug Res 1994 Aug 2-5;3:47 (abstract no. 46)

N.N. Zheng¹, S. Simasathiansophan¹, P.W. McQueen², L. Hurren², L. Evans³, S.F. Delaney¹, R. Penny² and D.A. Cooper^3
1Dept. Biotechnology, UNSW, Sydney, Australia, ²Centrefor Immunology, St. Vincent's Hospital, Sydney, Australia, ³National Centre in HIV Epidemiology & Clinical Research, UNSW, Sydney, Australia

This study was carried out 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 and if there is a relationship between SI/NSI virus and resistance. 175 people (ZDV intolerant) were recruited into the MRC/INSERM Alpha trial to test the efficacy and safety of high-dose (750 mg daily) versus low-dose (200 mg daily) ddI. ZDV resistant mutation at codon 215 of the RT gene was determined by selective PCR. Mutation occurred in 48 patients; 22 also showed wild type 215. 287 samples were SI phenotyped. At the start of the trial 59% were NSI. After 12 weeks ddI therapy NSI phenotype increased to 75%, declining again as therapy continued. Five patients were studied in detail. Their virus was ZDV resistant and ddI sensitive at the start of the trial. Sequential isolates became ddI resistant while remaining ZDV resistant. DNA sequencing revealed two possible novel mutations to ddI resistance. Although all patients entering the trial were classified as ARC or AIDS, not all the isolates were SI. A high percentage of NSI isolates at week 12 suggests that ddI may be useful for delaying the emergence of SI virus during the early stages of therapy. Although trends for individuals patients varied, in general there was stability of ZDV sensitivity and an increase in ddI resistance with time. This resistance may be conferred by novel mutations as well as known mutations at codons 74 and 184.

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1994-08-02
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