ANTIRETROVIRAL CHEMOTHERAPY OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTIONS OTHER THAN WITH AZIDOTHYMIDINE

The intense research effort to develop molecules with the ability to inhibit the replication of human immunodeficiency virus type 1 was greatly facilitated by the elucidation of the viral life cycle. This information engendered the production of novel antiretroviral agents that inhibit human immunodeficiency virus type 1 at different points in its replicative cycle. The nucleoside analogue 3'-azido-2',3'-dideoxythymidine (azidothymidine) inhibits reverse transcriptase, and it was the first compound tested in patients with the acquired immunodeficiency syndrome. Considerable knowledge of the activity and toxicity of this class of drugs has accumulated. Less well-characterized compounds inhibit human immunodeficiency virus type 1 binding and absorption to target cells, prevent the expression of viral genetic material critical for the construction of new infectious viral progeny, and inhibit the posttranslational modification of viral polypeptides. In additional, biologic response, modifiers act to restore immune function by a number of diverse mechanisms. The ultimate goal is the discovery of compounds capable of inducing a complete and permanent remission of infection.