HIV inhibitors: problems and reality.

The human immunodeficiency virus encodes three replication enzymes, which are required for a productive life-cycle. Currently, several anti-retroviral drugs are available for clinical use, and they are inhibitors of either the reverse transcriptase or the viral protease. The introduction of combination anti-retroviral therapy (HAART) changed the prognosis of HIV infection. However, current therapy is not able to eradicate the virus, only suppress it; therefore, long-term use of the drugs is required to keep the viral load under control. Most of the problems associated with the HIV therapy are the consequence of the necessarily long-term use of the drugs. The long-term effectiveness of current inhibitors as therapeutic agents is limited by the rapid development of drug-resistant variants. Furthermore, various side effects have been reported. These side effects include hypersensitivity, mitochondrial toxicity, lypodystrophy syndrome, insulin resistance and cardiovascular disorders. Further drug development is necessary to design new compounds that have efficacy similar to the currently used drugs in the management of HIV infection and that are potent against the resistant viruses but do not exhibit unwanted metabolic side effects.