Role of integrase inhibitors in the treatment of HIV disease

The introduction of highly active antiretroviral therapy (HAART) has produced a dramatic reduction in HIV-related mortality and morbidity among populations with widespread access to drugs. However, the increase in mutated HIV strains with reduced susceptibility to antiretroviral agents and the emergence of HAART-related side effects make it necessary to develop novel compounds characterized by activity against resistant viruses, a high genetic barrier to resistance and favorable pharmacokinetic and toxicity profiles. Integrase is a key enzyme in the life cycle of HIV and has represented an appealing target of antiretroviral therapy for several years. In 2006, after more than a decade of advances, pitfalls and disappointments, large clinical trials with integrase inhibitors in HIV-positive subjects have eventually begun.