Nuclear translocation as a novel target for anti-HIV drugs

During recent years, remarkable progress has been achieved in the treatment of patients infected with HIV. This progress involves not only the improvement of previously known drugs but also the introduction of new classes of anti-HIV agents. Currently, drugs targeting virus entry, reverse transcription, integration and maturation are either in clinical use or in the late stages of clinical development. Nonetheless, the high mutation rate of the virus and toxicity of the drugs, which become problematic during prolonged treatment regimens characteristic of anti-HIV therapy, drive the necessity to produce new drugs that will allow physicians to keep the virus at bay in patients on lifelong anti-HIV therapy. Ideally, such drugs would target a new step in the HIV life cycle, thus avoiding crossresistance with older compounds. One such new target for anti-HIV therapy is nuclear translocation--a process critical for HIV replication. In this article, the authors will review recent literature on the mechanisms of HIV nuclear import and will describe compounds that inhibit this step of HIV replication.