Entry inhibitors and their use in the treatment of HIV-1 infection

• Entry inhibitors are a diverse group of drugs targeting various stages of HIV entry.
• Maraviroc and enfuvirtide are approved for the treatment of infected patients.
• Identifying patients likely to respond to entry inhibitors can be complex.
• Resistance to enfuvirtide but not maraviroc shows ‘signature’ mutations.
• Entry inhibitors can be used in drug-sparing, salvage, and intensification regimens.

Entry of HIV into target cells is a complex, multi-stage process involving sequential attachment and CD4 binding, coreceptor binding, and membrane fusion. HIV entry inhibitors are a complex group of drugs with multiple mechanisms of action depending on the stage of the viral entry process they target. Two entry inhibitors are currently approved for the treatment of HIV-infected patients. Maraviroc, a CCR5 antagonist, blocks interactions between the viral envelope proteins and the CCR5 coreceptor. Enfuvirtide, a fusion inhibitor, disrupts conformational changes in gp41 that drive membrane fusion. A wide array of additional agents are in various stages of development. This review covers the entry inhibitors and their use in the treatment of HIV-infected patients.