HIV-1 entry inhibitors: recent development and clinical use

Curr Opin Virol. 2013 Feb;3(1):51-7. doi: 10.1016/j.coviro.2012.12.002. Epub 2013 Jan 3.


Purpose of review: This review provides an overview of HIV-1 entry inhibitors, with a focus on drugs in the later stages of clinical development.

Recent findings: Entry of HIV-1 into target cells involves viral attachment, co-receptor binding, and fusion. Antiretroviral drugs that interact with each step in the entry process have been developed, but only two are currently approved for clinical use. The small molecule attachment inhibitor BMS-663068 has shown potent antiviral activity in early phase studies, and phase 2b trials are currently underway. The postattachment inhibitor ibalizumab has shown antiviral activity in phase 1 and 2 trials; further studies, including subcutaneous delivery of drug to healthy individuals, are anticipated. The CCR5 antagonist maraviroc is approved for use in treatment-naïve and treatment-experienced patients. Cenicriviroc, a small-molecule CCR5 antagonist that also has activity as a CCR2 antagonist, has entered phase 2b studies. No CXCR4 antagonists are currently in clinical trials, but once daily, next-generation injectable peptide fusion inhibitors have entered human trials. Both maraviroc and ibalizumab are being studied for prevention of HIV-1 transmission and/or for use in nucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens.

Summary: Inhibition of HIV-1 entry continues to be a promising target for antiretroviral drug development.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Chemoprevention / methods
  • Clinical Trials as Topic
  • Cyclohexanes / pharmacology
  • Cyclohexanes / therapeutic use
  • Disease Transmission, Infectious / prevention & control
  • HIV Fusion Inhibitors / pharmacology*
  • HIV Fusion Inhibitors / therapeutic use
  • HIV Infections / drug therapy
  • HIV Infections / prevention & control
  • HIV-1 / drug effects*
  • HIV-1 / physiology*
  • Humans
  • Maraviroc
  • Organophosphates / pharmacology
  • Organophosphates / therapeutic use
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Triazoles / pharmacology
  • Triazoles / therapeutic use
  • Virus Internalization / drug effects*


  • Antibodies, Monoclonal
  • Cyclohexanes
  • HIV Fusion Inhibitors
  • Organophosphates
  • Piperazines
  • Triazoles
  • fostemsavir
  • ibalizumab
  • Maraviroc