Fifth International Congress Drug Therapy in HIV Infection 22-26 October, 2000 Glasgow, UK

Overview on the latest on genotype/phenotype and replicative fitness: the science

D.D. Richman
Departments of Pathology and Medicine, University of California San Diego, and San Diego Veterans Affairs Healthcare System, 9500 Gilman Drive, La Jolla, CA 92093–0679, USA

Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL4.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S4

HIV drug resistance develops when there are high levels of virus replication in the presence of suboptimal levels of antiviral drug. Suboptimal levels of drug may result from poor drugs, poor prescribing, pharmacological problems or poor patient adherence. HIV that has acquired drug resistance is more difficult to suppress with treatment, often resulting in yet higher levels of resistance with a broader range of cross-resistance. The genetics and enzymological mechanisms of resistance are well delineated although new insights continue.

Phenotypic and genotypic assays for resistance have moved from academic research labs into commercial service labs and are becoming incorporated in standard patient management. This progress is driving a new set of very practical questions for which answers are inadequate. Which assays and which laboratories have satisfactory performance characteristics and how are these measured and maintained? For phenotype assays, what fold change in susceptibility and for genotype assays, what change in mutational pattern predicts activity for a given antiretroviral drug? For different clinical situations is one assay more useful than another? Enzyme function and viral replicative capacity are impacted by resistance mutations. Will assays for these effects (loosely termed “fitness”) provide useful information for clinical management?

Data to partially address each of these questions have been generated. Defining what is not adequately answered will help direct more effective clinical research.

Presenting author: D.D. Richman

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2000-10-22
PL4-1

Originally published in AIDS Volume 14, 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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