Sixth International Congress Drug Therapy in HIV Infection 17-21 November, 2002 Glasgow, UK

Antiretroviral therapy changes the natural history of HIV infection, and this has resulted in dramatic improvements in HIV-related morbidity and mortality throughout the developed world. However, despite the current availability of 16 antiretroviral drugs approved for the treatment of HIV infection, current combination regimens have limitations. As many as 60% of patients may experience treatment failure of current antiretroviral regimens, due to dif- ficulties with adherence, toxicity and/or drug resistance. Newer drugs and drug combinations are needed to improve the ease of administration, tolerability, and antiretroviral activity (against both wild type virus and, in particular, drug-resistant virus) of the current antiretroviral drugs. Antiretroviral activity against drug-resistant viral strains may be improved by enhancing the pharmacokinetic properties of antiretroviral agents, identifying new agents in existing drug classes with increased inherent antiretroviral activity against drug-resistant virus, or developing agents in new drug classes with novel mechanisms of action. Promising agents are in development in existing classes of antiretroviral drugs: new nucleoside analogue reverse transcriptase inhibitors (nRTI), non-nucleoside analogue reverse transcriptase inhibitors (NNRTI), nucleotide analogue reverse transcriptase inhibitors (ntRTI), and protease inhibitors (PI). Many of these agents demonstrate in vitro activity against drug-resistant isolates and some demonstrate activity in clinical studies of treatment-experienced subjects. Antiretroviral compounds with new mechanisms of action would be expected to show antiretroviral activity, even against viral strains with decreased susceptibility to currently available drug classes. Promising agents are in clinical development that have new mechanisms of action: HIV entry inhibitors (e.g., targeting CD4 attachment, chemokine receptor attachment, or fusion of viral and target cell membranes) and HIV integrase inhibitors. Some of these newer agents demonstrate antiretroviral activity, both in vitro and in clinical studies of treatment-experienced subjects. Additional targets (e.g., viral uncoating, RNAase H enzyme, TAT protein, budding) provide opportunities for future drug development. Further improvements in HIV therapy will result from continued, coordinated efforts in both basic and clinical research.

Presenting author: Roy Gulick

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1 Weill Medical College of Cornell University, New York, USA

2002-11-17
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