Second International Congress Drug Therapy in HIV Infection 18-22 November 1994 Glasgow, UK

AZT RESISTANCE AND DISEASE PROGRESSION IN THE CONCORDE TRIAL

F. Brun-Vézinet, S. Kaye*, F. Ferchal, C. Loveday*, C. Buffet-Janvresse, R. Tedder*, and the Concorde Coordinating Committee;
Drug Resistance Working Group, Virology, ANRS, France; * Division of Virology, UCL London Medical School, UK.

Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.5
AIDS 1994, Vol. 8 (Suppl. 4);S5

OBJECTIVES: To evaluate in patients on Concorde trial a possible correlation between AZT resistance with clinical progression, changes in CD4 counts and RNA viral load.

PATIENTS: Progressors were matched with non-progressors for time on AZT, entry CD4 cell number and p24 antigenemia status at the enrolment.

SPECIMENS: Three to five stored specimens per patient were studied: pretreatment, at months 3 and 6, then at the time of the clinical event:t 3 mo and 6-9 mo before the clinical event.

METHODS: The in vitro sensitivity of the isolates (IC₅₀, IC90) was determined by a PBMC-RT based assay. Mutations at codons 41,67,70, 215,219 were detected by selective PCR on DNA extracted from PBL or cultured lymphocytes. The RT coding region was sequenced in selected cases. Using in-house methods developed in R. Tedder's laboratory, serum HIV-1 RNA was quantified by an immunocapture PCR, and genomic resistance in the same RNA was quantified by a point mutation assay (PMA).

RESULTS: In the french case-control study high level of resistance (IC₅₀≥1μM) was a rare event in the patients. Mutation at codon 215 was systematically associated with decrease in AZT susceptibility (IC₅₀≥0.05μM).Single mutation at codon 70 was very common, not predictive of occurence of resistance and could be observed in pretherapy specimens. The analysis of this case control study, based on the PCR results, showed a significant association (p=0.001)between emergence of mutation at codon 215 and clinical progression. Resistant viral populations were detected at least 6-9 months before the clinical event. Statistical analyses of the correlation between AZT resistance and clinical progression, adjusted on CD4 cell counts and viral load will be presented. These results will also be extended to those of the U.K. case control study.

Presenting author: F. Brun-Vézinet

1994-11-18
5.5

Originally published in AIDS Volume 8, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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