title: Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry.
abstract: 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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 35294-2050, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Kilby
authors.forename: S
authors.initials: S
authors.lastname: Hopkins
authors.forename: T M
authors.initials: TM
authors.lastname: Venetta
authors.forename: B
authors.initials: B
authors.lastname: DiMassimo
authors.forename: G A
authors.initials: GA
authors.lastname: Cloud
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Alldredge
authors.forename: E
authors.initials: E
authors.lastname: Hunter
authors.forename: D
authors.initials: D
authors.lastname: Lambert
authors.forename: D
authors.initials: D
authors.lastname: Bolognesi
authors.forename: T
authors.initials: T
authors.lastname: Matthews
authors.forename: M R
authors.initials: MR
authors.lastname: Johnson
authors.forename: M A
authors.initials: MA
authors.lastname: Nowak
authors.forename: G M
authors.initials: GM
authors.lastname: Shaw
authors.forename: M S
authors.initials: MS
authors.lastname: Saag
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000097:blood* / Q000502:physiology* / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D006207:Half-Life; D006801:Humans; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000097:blood* / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D000077560:Enfuvirtide