[Non-nucleoside antiretroviral agents]

Antiviral agents, other than nucleoside reverse transcriptase inhibitors, are currently being developed. Some have been marketed. Most of these new drugs are protease inhibitors which inhibit the formation and release of new infecting virions at the end of the intracellular cycle of the human immunodeficiency virus. Saquivanir, ritonavir, and indinavir are among the most widely studied. Non-nucleoside reverse transcriptase inhibitors (nevirapine is the leading product) include several components called TIBO or TIBO-like. These drugs have the advantage of good tolerance but resistance may develop early when they are given alone. Clinical trials aimed at preventing virus-cell fusion have not been successful in vivo. Other therapeutic approaches, including antisense oligonucleotids, ribozymes, and TAT or REV gene inhibitors are being explored. Several trials focusing on therapeutic strategy are being conducted using combinations of drugs. The objective is to use both non-nucleoside and nucleoside reverse transcriptase inhibitors together with antiproteases. Certain combination protocols using 3 or more antiviral agents have shown a synergetic effect and reduced or delayed resistance. Finally, the role of immunomodulation and immunotherapy is under investigation.