The identification of viral and cellular drug targets is essential for fueling the drug and vaccine development pipeline. Early drug discovery efforts concentrated on a relatively small number of viral targets: HIV reverse transcriptase (an enzyme that catalyzes the synthesis of viral DNA within infected cells from the RNA template carried by infectious virions) and HIV protease (an enzyme that cleaves and processes viral precursor proteins allowing virion maturation). Treatment regimens containing combinations of reverse transcriptase and protease inhibitors, commonly known as highly active antiretroviral therapy (HAART), revolutionized the treatment of people with HIV by markedly lowering viral load and decreasing the incidence of AIDS-associated opportunistic infections. Many patients receiving HAART nevertheless suffer metabolic abnormalities and drug toxicities, have difficulty adhering to the complex drug regimens, and develop strains of HIV resistant to therapy.
Thus, additional viral and cellular targets are now being extensively studied and therapies targeting HIV integrase, various steps in the virus entry process, and virion maturation have been examined in clinical trials in recent years. Still in the early stages of preclinical investigation are potential inhibitors of Vif/APOBEC; ESCRT I, II, and III (virus assembly); and TRIM-5 alpha (virus uncoating).
Currently, NIAID is supporting HIV-targeted intervention research in the following areas:
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Last Updated April 17, 2008