Integrase inhibitors in the treatment of HIV-1 infection.

Agents active against HIV type 1 (HIV-1) that target the viral integrase by inhibiting the strand transfer step of integration have now entered the clinical arena. Raltegravir is the first in this new class. Clinical trials in treatment-experienced and in treatment-naive patients have shown that raltegravir-containing regimens have potent antiretroviral activity and are well tolerated. Drug resistance emerges relatively frequently in patients who fail therapy and is associated with mutations in the gene encoding the integrase enzyme. Although such mutations often confer cross-resistance to other integrase inhibitors, newer agents in development, such as S/GSK1349572, show promise as potential second-generation integrase inhibitors. Given their potency, safety and novel mechanism of action, integrase inhibitors represent an important advance in HIV-1 therapy.