Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry

T-20, a synthetic peptide corresponding to a region of the transmembrane subunit of the HIV-1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administered intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected adults in four dose g...

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Bibliographic Details
Published in:	Nature medicine Vol. 4; no. 11; pp. 1302 - 1307
Main Authors:	Kilby, J. Michael, Saag, Michael S, Hopkins, Sam, Venetta, Thomas M, DiMassimo, Betty, Cloud, Gretchen A, Lee, Jeannette Y, Alldredge, Leslie, Hunter, Eric, Lambert, Dennis, Bolognesi, Dani, Matthews, Thomas, Johnson, M. Ross, Nowak, Martin A, Shaw, George M
Format:	Journal Article
Language:	English
Published:	United States 01-11-1998
Subjects:	Adult AIDS/HIV Anti-HIV Agents - blood Anti-HIV Agents - pharmacokinetics Anti-HIV Agents - therapeutic use CD4 Lymphocyte Count Dose-Response Relationship, Drug Half-Life HIV Envelope Protein gp41 - blood HIV Envelope Protein gp41 - physiology HIV Envelope Protein gp41 - therapeutic use HIV Infections - drug therapy HIV Infections - virology HIV-1 - drug effects HIV-1 - isolation & purification HIV-1 - physiology Human immunodeficiency virus 1 Humans Metabolic Clearance Rate Peptide Fragments - blood Peptide Fragments - therapeutic use Virus Replication - drug effects
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Summary:	T-20, a synthetic peptide corresponding to a region of the transmembrane subunit of the HIV-1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administered intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected adults in four dose groups (3, 10, 30 and 100 mg twice daily). There were significant, dose-related declines in plasma HIV RNA in all subjects who received higher dose levels. All four subjects receiving 100 mg twice daily had a decline in plasma HIV RNA to less than 500 copies/ml, by bDNA assay. A sensitive RT-PCR assay (detection threshold 40 copies/ml) demonstrated that, although undetectable levels were not achieved in the 14-day dosing period, there was a 1.96 log10 median decline in plasma HIV RNA in these subjects. This study provides proof-of-concept that viral entry can be successfully blocked in vivo. Short-term administration of T-20 seems safe and provides potent inhibition of HIV replication comparable to anti-retroviral regimens approved at present.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1078-8956 1546-170X
DOI:	10.1038/3293