According to the World Health Organization there are currently 96,000 cases of AIDS reported worldwide. It is estimated that by 1992 the number of cases will have increased to 1.2 million. AIDS and AIDS Related Complex (ARC) are caused by infection with retrovirus designated HIV which includes the subtypes HIV-1 and HIV-2. HIV exerts a profound cytopathic effect on the CD4+ helper/inducer T-cells, devastating the function of the immune system. HIV infection also results in neurological deterioration and ultimately death of the infected individual. The field of viral chemotherapeutics has developed in response to the need for agents effective against retroviruses, particularly HIV. There are many ways in which an agent can exhibit anti-retroviral activity, one of which is through inhibition of viral replication. For example the HIV virus requires at least four viral proteins for replication: Reverse Transcriptase (RT), protease, the transactivator protein TAT, and the REV protein. Anti-retroviral agents such as AZT or ddC are known to be RT inhibitors. Anti-viral agents such as TAT inhibitors would act at a different stage of the viral life cycle. HIV replication in latently infected CD4+ lymphocytes is induced when the cells are stimulated to proliferate by cytokines or mitogens. The viral switch from latency to active replication requires the regulatory gene products TAT and REV. The TAT protein transactivates the HIV-LTR promoter and amplifies viral replication many thousand fold. The TAT responsive sequence is mapped within the LTR sequence. Compounds which have anti-TAT activity will thus arrest HIV at the latent stage of viral infection by preventing replication of the provirus that is integrated into the host cell chromosome. Anti-TAT agents are thus useful for therapeutically treating patients infected with HIV including AIDS and ARC patients or asymptomatic carriers.
USPTO Backgrounds
USPTO Backgrounds