Novel targets for anti-retroviral therapy

Novel targets for the management of HIV infection have become increasingly relevant in view of extensive drug resistance, side effects and high pill burden of some of the conventional anti-retroviral agents. Structure based drug design using X-ray crystallography, nuclear magnetic resonance, and mass spectrometry have lead to the identification of novel class of drugs targeting new stages of HIV life cycle. These agents include chemokine receptor antagonists and the integrase inhibitors which were recently approved for HIV treatment, as well as numerous other agents directed to previously untested targets such as the maturation inhibitors, zinc finger inhibitors, pharmacological CDK inhibitors, Tat-TAR interaction inhibitors, anti-CD4 monoclonal antibody, antisense oligonucleotides, oxidisers of the HIV lipid envelope and agents acting on the proviral DNA. Use of new agents with novel mechanism of action requires the development of new laboratory assays to detect viral tropism and new resistance mutations. Despite the new developments providing hope to patients and clinicians in the fights against HIV, eradication of the disease still remains elusive. This review discusses issues surrounding the development of these new agents.