Current state-of-the-art in preclinical and clinical development of novel non-nucleoside HIV-1 reverse transcriptase inhibitors

Abstract

In spite of the tremendous advance in our understanding of the HIV-1 life cycle and of the molecular mechanisms underlying its pathogenesis, it is still not possible to fully control the HIV-1 infection for long periods of time, not to mention eradicate it. However, as it is still unclear whether an effective vaccine could be developed in a short time, therapeutic approaches based on the combination of different potent antiviral drugs are now thought to be the best option for the control of HIV-1 infection in patients. For this reason, development of novel molecules that are safer, more potent and less sensitive to drug resistance than available drugs is mandatory. Among the currently exploited anti-HIV drugs, non-nucleoside reverse transcriptase inhibitors play a major role. This review will summarise the most recent advances and evolutionary trends for this class of anti-HIV drugs.

Keywords::

• AIDS
• HAART
• HIV-1
• non-nucleoside inhibitors
• structure–activity relationships

Acknowledgments

Work in the authors’ laboratories has been partially supported by Italian Ministero della Salute – Istituto Superiore di Sanita’ – Fourth National Research Programme on AIDS (grant no. 40C.8 and no. 40D.46) and Fifth National Research Programme on AIDS (grant no. 40F.48 and no. 40F.78). The authors thank the Italian MIUR (PRIN2004) for partial support. The authors declare no conflict of interests.

Notes