The Body Covers: The 6th Conference on Retroviruses and Opportunistic Infections
Late Breaker No. LB13: Safety, Pharmacokinetics, and Antiviral Activity of T-20 as a Single Agent in Heavily Pre-Treated Patients
February 4, 1999
A new and potentially exciting agent is T-20, a 36 amino acid peptide that acts differently in inhibiting HIV replication than do existing classes of drugs. Its mechanism of action relates to its binding to a protein on the viral glycoprotein coat that becomes exposed after virus attaches to the host cell. By inhibiting the action of this glycoprotein, which is necessary to facilitate the intimate association of virus to host cell surface so that virus can enter the cell, viral infection is prevented. Drug must be delivered parenterally because its protein (peptide) composition would be digested by gastric juices. This study evaluated both intermittent subcutaneous dosing twice a day, or by continuous subcutaneous dosing facilitated by a constant-infusion pump.
The study enrolled 78 patients with plasma viral load >5000 copies/ml in a multicenter randomized open-label phase-2 clinical trial. Of these 78 patients, 77 reported heavy antiretroviral experience (mean number prior ARVs = 9) and 98% were protease inhibitor experienced (mean number of prior PIs = 3). T-20 was given over a 28 day treatment period to six groups of patients representing T-20 doses ranging from 12.5 - 200 mg per day, and patients were given the option of either continuing their stable antiretroviral regimen (59%) or using no other therapy at all (41%). The mean baseline CD4 was 117 and viral load 5.0 log (100,000 copies).
Even though antiviral benefit was observed in all doses during the 28 day treatment period, the benefit was clearly dose related. The highest dose tested (100 mg twice daily) achieved a drop of 1.6 log in viral load, but was not sustained at the end of the treatment period. Adverse effects (AE) were minimal: no grade 3 or 4 AEs and only two patient withdrawals (one due to infusion site pain and the other due to generalized rash). Mostly due to the inconvenience of having to wear a pump for twenty four hours each day, 14 patients from the continuous infusion groups switched to intermittent dosing during the course of the study. Because intermittent dosing was as effective as continuous dosing, subsequent studies will examine the intermittent subcutaneous route of administration.
Authored by: J. Lalezari, J. Eron, M. Carlson, R. Arduino, J. Goodgame, C. Cohen, L. Jones, J. Gleavy, A. Dusek, T. Venetta, E. Dimassimo, and S. Hopkins for the TRI-003 Study Group
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