Combination therapy with reverse transcriptase and protease inhibitors is the most common current treatment of HIV-1 infection.Despite the success of this therapy,it has adverse effects and drug resistant HIV-1 strains emerged.A new class of antiviral agents is in development,the entry inhibitors,which act extracellularly preventing viral entry into target cells.Each of the main steps in the HIV-1 entry process can be a target for entry inhibitors.The ones currently under development fall into three categories:gp120-CD4 binding inhibitors,gp120-co-receptors binding inhibitors,and membrane fusion inhibitors,which interfere with gp41 conformational changes.Fusion inhibitors are the leading compounds,one of them,enfuvirtide,being already approved for clinical applications.