T-20: Entirely New Antiretroviral
A drug which works against HIV by an entirely new mechanism of action has shown clear antiviral activity in a small proof-of-concept human trial.T-20, developed from virology knowledge gained through influenza research, is a 36-amino-acid peptide designed to block a critical step in the process by which HIV binds to and enters cells. The data showing antiretroviral activity in humans was first presented September 16 at the Infectious Disease Society of America 35th Annual Meeting in San Francisco (IDSA '97) .
Volunteers received the drug in four different doses, 3 mg, 10 mg, 30 mg, and 100 mg, every 12 hours, for 14 days. The highest dose group had a viral load decrease of at least 1.5 logs. (But all four patients who received this dose had their viral load go below the 500-copy limit of the test, so the actual decrease was probably greater.) A dose response was found, with the next lower dose (30 mg) having only a 0.48 log viral load decrease. The high-dose group had a CD4 count increase of 52 -- but the real improvement may be larger, since this change was measured after only 14 days, not enough time for the counts to fully recover. All four volunteers at the high dose had increased appetite and felt better.
No side effects are known.
T-20 has one important disadvantage: it must be injected, either twice a day or continuously (which would probably be better, judging from the 2.7-hour half life of the drug in the body). Today patients can use a small electronic pump, like wearing a pager, which provides continuous or other programmed drug injections.
What is still not known is whether T-20 will be tolerable and effective in long-term use.
The researchers below are at the University of Alabama at Birmingham, and at Trimeris, Inc., in Durham, North Carolina.
References
1. M. Saag, L. Alldredge, M. Kilby, and others. A Short-Term Assessment of the Safety, Pharmacokinetics, and Antiviral Activity of T-20, An Inhibitor of gp41 Mediated Membrane Fusion. IDSA 35th Annual Meeting, San Francisco, September 16, 1997 [abstract #771].
