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

IN VITRO SELECTION OF HIV-1 VARIANTS RESISTANT TO 3TC AND A SECOND REVERSE TRANSCRIPTASE INHIBITOR

Int Wkshop HIV Drug Res 1994 Aug 2-5;3:34 (abstract no. 33)

N. Cammack, M.G. Goulden, K.C. Viner, P. Hopewell, C.R. Penn and J.M. Cameron
Department of Virology, Glaxo Research and Development, Greenford, UB6 OHE, UK

The nucleoside analogue, 3TC™, is a selective inhibitor of reverse transcriptase (RT) that has potent antiviral activity in vitro, and is currently in Phase II/III combination trials with AZT. An amino acid change at codon 184 in the YMDD motif of RT is associated with the development of high-level resistance to this drug in vitro and in vivo. The potential for 3TC™-resistant HIV-1 variants to arise during 3TC™ monotherapy or combined treatment of AZT-therapy experienced and naïve patients was investigated. An AZT-resistant clinical HIV-1 isolate was serially passaged in vitro using 3TC™ without maintained AZT drug pressure. This HIV-1 variant demonstrated 3TC™-resistance with restored susceptibility to AZT as has previously been described. An HIV-1 variant passaged in nevirapine with maintained 3TC™ drug pressure revealed a virus with demonstrable phenotypic resistance to both drugs. Genotypic characterisation of these HIV-1 variants is under way and will be reported. The results have implications for the treatment of patients with a combination of 3TC™ and other HIV inhibitors.

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1994-08-02
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