From Anti-HIV Agents to Anti-AIDS Chemotherapy: A Critical Appraisal

Num erous compounds have been reported to inhibit the replication of hum an immunodeficiency virus (HIV) in vitro.1’2 Yet, only three agents have at this m om ent been formally licensed (in the U.S.A.) for clinical use in the treatm ent of AIDS. These are zidovudine (3&s;-azido-2&s;, 3’-dideoxythymidine, azidothymidine, AZT), 3didanosine (2&s;, 3-dideoxyinosine, DDI)4andzalcitabine (2&s;, 3-dideoxycytidine, DDC) .5The basic strategies and molecular targets for anti-HIV therapy have been repeatedly reviewed, starting from 1985, thus shortly after HIV had been identified as the causative agent of AIDS.6-11 The replicative cycle of HIV comprises a num ber of steps which could be considered as adequate targets for chem otherapeutic intervention (Figure 1.1). In fact, HIV follows a replicative pathway that is similar to that of the classical cytolytic RNA viruses, except for the reverse transcriptase (step 4) and integrase (step 5), which lead to the form ation and integration of the proviral DNA into the cellular DNA genome. Most of the substances which have been identified as anti-HIV agents can be allocated to one of the ten classes of HIV inhibitors, according to the stage at which they interfere with the HIV replicative cycle (Table 1.1).