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 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.
Kilby
J M
JM
Department of Medicine, University of Alabama at Birmingham, 35294-2050, USA.
Hopkins
S
S
Venetta
T M
TM
DiMassimo
B
B
Cloud
G A
GA
Lee
J Y
JY
Alldredge
L
L
Hunter
E
E
Lambert
D
D
Bolognesi
D
D
Matthews
T
T
Johnson
M R
MR
Nowak
M A
MA
Shaw
G M
GM
Saag
M S
MS
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*
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D000077560:Enfuvirtide