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 transmembra ne subunit of the HIV 1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administere d intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected a dults in four dose groups (3, 10, 30 and 100 mg twice daily). There we re significant, dose-related declines in plasma HIV RNA in all subject s 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 copi es/ml) demonstrated that, although undetectable levels were not achiev ed in the 14-day dosing period, there was a 1.96 log(10) median declin e in plasma HIV RNA in these subjects. This study provides proof-of-co ncept that viral entry can be successfully blocked in vivo. Short-term administration of T-20 seems safe and provides potent inhibition of H IV replication comparable to anti-retroviral regimens approved at pres ent.