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

PHENOTYPIC AND GENOTYPIC CHARACTERIZATION OF HIV-1 VIRAL ISOLATES FROM PATIENTS TREATED WITH COMBINED AlT AND DELAVIRDINE MESYLATE (DLV) THERAPY

Int Wkshop HIV Drug Res 1994 Aug 2-5;3:42 (abstract no. 41)

L.K. Wathen, W.W. Freimuth, D.H. Batts, S.R. Cox
Upjohn Laboratories, Kalamazoo, MI 49007, USA

Thirty-four AZT experienced patients with CD4 counts between 200 and 500/mm³ were treated for up to 32 weeks with a combined regimen of oral AZT 200 mg TID and DLV. The five DLV dose regimens tested were 100 mg QID, 200 mg QID, 300 mg QID, 300 mg TID and 400 mg TID. The average steady state plasma concentrations for these DLV regimens were 4.3 µM, 7.6 µM, 10 µM, 13 µM and 31 µM respectively. At weeks 6, 12, 16, 24 and 32 of treatment, samples were taken for phenotypic and genotypic characterization. The average DLV IC₅₀ at baseline was 0.017 µM. The average AZT IC₅₀ at baseline was 0.833 µM. Sufficient virus for typing was recovered pre and post therapy in 16 of the 34 patients. 81% (13/16) of the patients had a DLV IC₅₀ within achievable blood levels throughout the study. Thirteen treatment-emergent amino acid substitutions have been seen in the RT gene (aa 15-250) to date. The most prevalent amino acid substitution was Lys103Asn. This mutation was found in 10 out of 14 genotyped subjects. The Pro236Leu mutation was only seen in one of fourteen, and coincident with that mutation had the highest DLV IC₅₀ seen at six weeks (6.639 µM). There were no aa181 or aa188 mutations. With increasing DLV IC₅₀ there was a decrease in AZT IC₅₀, despite the pre-existence of a Thr215Tyr/Asn in 4/14 and the treatment emergence of Lys219Gln in 2/14. Further studies will be needed to determine the time course of change in DLV IC₅₀ and full characterization and clinical significance of the resulting mutations.

Download PDF of this abstract.

1994-08-02
41

Copyright © 1994 - International Medical Press Ltd. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the International Medical Press Ltd. 2-4 Idol Lane, London EC3R 5DD UK.