New perspectives for the treatment of HIV infections

Eleven compounds have now been licensed for the treatment of HIV (human immunodeficiency virus) infections: the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) zidovudine (ZDV, AZT), didanosine (DDI), zalcitabine (DDC), stavudine (D4T) and lamivudine (3TC), the nonnucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and delavirdine, and the protease inhibitors saquinavir, ritonavir, indinavir and nelfinavir. Several other compounds that interact with the reverse transcriptase or protease or other targets of the viral replication cycle are in clinical or preclinical development. High expectations are vested in the acyclic nucleoside phosphonates PMEA and PMPA (which have proved clearly efficacious against HIV infections in phase II/III and phase I/II trials, respectively) and the bicyclam derivatives, which have recently been shown to block HIV infection through interference with the viral co-receptor CXCR4 (fusin). It has become increasingly clear that only the concomitant use of several anti-HIV agents combined can completely suppress HIV replication and offer the potential for a complete cure. To this end, the different compounds should be administered from the start at sufficiently high doses, and treatment should be started as soon as possible after the infection. Under these conditions, HIV-drug resistance development could be prevented, and progression to AIDS, arrested. Whether this procedure would also be able to eradicate the virus from the organism still needs to be proven.