Background: T-1249 is a peptide fusion inhibitor that has shown potent antiviral activity over 14 days of administration in fusion inhibitor naïve HIV-infected adults. In vitro studies suggest that T-1249 is active against most HIV isolates resistant to enfuvirtide (ENF). This study evaluated the short-term safety and antiretroviral activity of T‑1249 in 50 patients failing a regimen containing ENF.

Methods: Patients were HIV-1 infected adults participating in a phase II or III ENF study who were receiving ENF and a stable background antiretroviral regimen and demonstrated two consecutive plasma HIV RNA values between 5,000 and 500,000 copies/ml. Patients discontinued ENF after the evening dose and the next morning added 192 mg/day of T‑1249 subcutaneously to the unchanged background regimen for 10 days. The data presented here reflect the results of the planned interim analysis of the first 25 patients. Enrollment into the study has now been completed.

Results: Median baseline HIV RNA and duration of prior ENF treatment were 5.0 log₁₀ copies/ml and 70 weeks, respectively. Median time on ENF since virological failure prior to enrollment in T1249-102 was 56 weeks (range 28-136). All 24 (96%) patients whose plasma virus could be amplified at baseline demonstrated ENF-resistance mutations and/or decreased phenotypic susceptibility to ENF and were included in the Intent-to-Treat population.  No patient discontinued T-1249 prematurely. The median (95% CI) log₁₀ HIV RNA change from baseline at Day 11 was –1.12 (–1.50, –0.83). Fifteen (63%) patients had at least a 1.0 log₁₀ and 19 (79%) patients had at least a 0.5 log₁₀ drop in HIV RNA at Day 11. Patients failing ENF for 24-48 weeks appeared to have better responses (7/7 patients achieved >1 log₁₀ decrease in HIV RNA; median Day 11 decrease in HIV RNA –1.6 log₁₀) than those who had been failing for >48 weeks (8/17 achieved >1 log₁₀ decrease in HIV RNA; median Day 11 decrease in HIV RNA –0.94 log₁₀).  There were no serious adverse events judged possibly related to T-1249.

Conclusions: The results of this interim analysis suggest that T‑1249 demonstrates potent short-term suppression of plasma HIV RNA in most patients who harbor ENF-resistant viruses.