The Body Covers: The 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy
T-1249 Retains Potent Short-Term Antiviral Activity in Patients Who Have Failed a Regimen Containing T-20
September 14, 2003
The arrival of the fusion inhibitor T-20 (enfuvirtide, Fuzeon) has led to a lot of excitement about the potential to reestablish suppression, especially for patients with few other drug options. However, it has become clear that after about one year approximately 50 percent of the patients who entered T-20 studies had eventual viral escape and rebound despite their new regimen with T-20. Clearly then, we need to develop additional new drugs that can work against T-20-resistant virus. Fortunately, such a compound has already been identified and the data for T-1249 were updated in this presentation.Reference
T-1249, like T-20, interferes with one of the final steps of viral entry, just prior to the actual fusion of the HIV wall and the cell membrane. Early in its development, it was also shown to have predicted activity against HIV that has become resistant to T-20.
An initial look at this study of those with rebound while on T-20 based regimens was shown earlier this year at the Retrovirus conference. This presentation summarized the final results of those who went from T-20 to T-1249. To enter this study, patients had to have a viral load between five and 500,000 copies while on a T-20-containing regimen.
Based on resistance assays, evidence of resistance to T-20 was found in patients who experienced viral rebound while on it.
This study did a simple substitution design, replacing the T-20 with T-1249 in 53 people for 10 days, at which point the rest of the regimen could be altered.
The initial viral load at entry was about 100,000, and the CD4 count was about 86. This group typically had been experiencing rebound despite the use of T-20 for just over one year when this study was enrolled, and almost all the patients had evidence of reduced susceptibility to T-20 at baseline. By day 10, there was a mean 1.26 log drop in the viral load; 73 percent had at least a one log decline at this point.
It was not entirely clear that continued replication on the T-20 regimen led to predictable resistance to T-1249 -- while there was some correlation, there were many exceptions as well. Few side effects were reported. While there were injection site reactions, this was reported in just 64 percent of those on this agent, somewhat less often than what is reported on T-20 studies. There was no clear evidence of other side effects after this 10-day study design.
The implications of these data are clear. There remains a need for new drugs that retain activity despite currently resistant virus. While we can often do well with the current agents, there remain some for whom there are still not enough new and active drugs to reestablish control of viremia. These data clearly support that T-1249 has potential for future development, given the encouraging balance of both efficacy against T-20-resistant virus, plus relative safety. Future studies will be anxiously awaited for this new compound.
View the slide show of the abstract covered in this article.
Authored by: J. P. Lalezari, N. Bellos, G. Richmond, K. Sathasivam, C. Cohen, R. Myers, D. Henry, C. Raskino, Y. Zhang, B. Spence, R. Demasi, D. Miralles
Affiliations: Quest, SF, CA; PP, Dallas, TX; PP, Ft Lauderdale, FL; E Taylor Med Center, Washington, DC; CRI, Boston, MA; PP, Phoenix, AZ; UPenn, Phil, PA; Roche, Welwyn, United Kingdom; Trms, Durham, NC
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