Third International Congress Drug Therapy in HIV Infection 3-7 November 1996 Glasgow, UK

VIRAEMIA AND RESISTANCE FROM IN VITRO TO IN VIVO

R S Tedder, P. Balfe, S Kaye
Department of Virology, UCL Medical School, Windeyer Building, 46 Cleveland Street, LONDON W 1P 6DB

Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 4.2
AIDS 1996, Vol. 10 (Suppl. 2);S3

The response of viral plasma RNA levels to antiviral therapy remains the best immediate measure of drug efficacy and development of drug resistance. RNA quantification using commercial reagents, however, is based solely on Glade B virus sequences. Patients with non-B viruses are being recruited into UK studies and this finding and the emerging need to conduct studies outside UK/Europe justify the development of alternative strategies for RNA measurement utilising genomic targets other than gag. Strategies for approaching this problem will be described.

In one current clinical study in the United Kingdom, 15% of patients enrolled were considered epidemiologically to be infected with non-Glade B strains. This has been confirmed by sequencing and the data will be presented. The viral RT provides a novel genetic background against which drug induced mutations may evolve and is an additional challenge for assays currently used for the detection and quantification of resistance-associated point mutations.

Point mutation assays (PMA) can be run on nucleic acid sequences derived from plasma RNA, PBMC DNA and culture viral RNA. The correlation between the genomic resistance in these three analytes and phenotypic resistance is good, allowing the use of PMA to predict and monitor the evolution of drug resistance in vivo. The closest correlation is seen between genomic resistance and phenotypic resistance in culture, but in spite of selective pressures of virus isolation and culture, resistance measures ex vivo, including from plasma RNA and PBMC DNA, predict closely the rescue of phenotypically-resistant virus in culture. On a population basis PMA can also define the load of resistant virus during therapy, in trial situations this may be relevant to estimating the biological impact of virus resistance of developing in vivo. Data will be presented in support of this concept.

Presenting author: R S Tedder

1996-11-03
4.2

Originally published in AIDS Volume 10, Supplement 2 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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