Basic science priorities for therapeutics research.

Abstract

For more than 10 years, drug discovery efforts have concentrated on relatively few viral targets: reverse transcriptase (RT) and protease (PR). While viral load can be reduced by combining RT and PR inhibitors in regimens referred to as highly active antiretroviral therapy (HAART), recent studies suggest that many treatment failures occur because of the development of drug resistance and lack of adherence to complicated and often toxic regimens. Recently, new classes of agents directed at the virus binding and entry process have entered the development pipeline, with one such agent now approved for use in patients with HIV. Early data suggests, however, that the development of resistance will continue to be a problem as new agents are introduced into HAART regimens. With regard to the immune system, it has become clear that the damage caused by HIV infection is only partially reversed by HAART. Vaccination represents a major new immunologic approach to complement drug treatment. Thus, while advances continue to be made, there remains an urgent need for the identification of new host and viral targets, novel drugs and delivery systems, and immunologic approaches to address the dual problems of drug resistance and toxicity. To address this need, the Division of AIDS has established basic science priorities in the following areas of therapeutics research: host and viral targets, inhibitors, vaccines, innate immunity, viral reservoirs, and gene therapy.