Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Feb;3(1):51-7.
doi: 10.1016/j.coviro.2012.12.002. Epub 2013 Jan 3.

HIV-1 entry inhibitors: recent development and clinical use

Timothy J Henrich  1 , Daniel R Kuritzkes
Affiliations
Review

HIV-1 entry inhibitors: recent development and clinical use

Timothy J Henrich et al. Curr Opin Virol. 2013 Feb.

Abstract

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.

PubMed Disclaimer

References

    1. Kwong PD, Wyatt R, Sattentau QJ, Sodroski J, Hendrickson WA. Oligomeric modeling and electrostatic analysis of the gp120 envelope glycoprotein of human immunodeficiency virus. J Virol. 2000;74:1961–1972. - PMC - PubMed
    1. Weiss CD, Levy JA, White JM. Oligomeric organization of gp120 on infectious human immunodeficiency virus type 1 particles. J Virol. 1990;64:5674–5677. - PMC - PubMed
    1. Chan DC, Fass D, Berger JM, Kim PS. Core structure of gp41 from the HIV envelope glycoprotein. Cell. 1997;89:263–273. - PubMed
    1. Daar ES, Li XL, Moudgil T, Ho DD. High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates. Proc Natl Acad Sci U S A. 1990;87:6574–6578. - PMC - PubMed
    1. Schooley RT, Merigan TC, Gaut P, Hirsch MS, Holodniy M, Flynn T, Liu S, Byington RE, Henochowicz S, Gubish E, et al. Recombinant soluble CD4 therapy in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase I-II escalating dosage trial. Ann Intern Med. 1990;112:247–253. - PubMed

MeSH terms