Abstract LB5 - A Controlled Phase II Trial Assessing Three Doses of T-20 in Combination with Abacavir, Amprenavir, Low Dose Ritonavir and Efavirenz in Non-Nucleoside Naïve Protease Inhibitor Experienced HIV-1 Infected Adults

LB5 A Controlled Phase II Trial Assessing Three Doses of T-20 in Combination with Abacavir, Amprenavir, Low Dose Ritonavir and Efavirenz in Non-Nucleoside Naïve Protease Inhibitor Experienced HIV-1 Infected Adults

J. Lalezari*¹, J. Drucker², R. Demasi², S. Hopkins², and M. Salgo³
¹Quest Clin. Res., San Francisco, CA;²Trimeris, Inc., Durham, NC; and³Roche, Inc., Nutley, NJ

Background:T-20 is the first of a novel class of antiretroviral agents, fusion inhibitors, in development for the treatment of HIV-1 infection. We report Week 16 planned interim results of a controlled Phase II open label, randomized, dose-comparison study in adults with HIV-1 infection who have been treated with at least one protease inhibitor but not with non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Objectives:To evaluate the safety and activity of three doses of T-20 in combination with a fixed regimen of oral antiretrovirals.

Design:Seventy-one subjects were enrolled in one of four treatment groups: ARV [A, n=19](abacavir 300mg BID, amprenavir 1200mg BID, ritonavir 200mg BID, and efavirenz 600mg QD), or ARV plus 50[B, n=16], 75[C, n=20], or 100[D, n=16]mg T-20 BID given subcutaneously.

Results:Median overall baseline plasma HIV-1 RNA (pVL) and CD4+ cell count were 4.27 log₁₀and 232 cells/mm3, respectively. Mild to moderate local injection site reactions were the most frequently reported T-20 related adverse events, occurring in 65% of patients on T-20. The incidence of other clinical adverse events and laboratory abnormalities was similar between the T-20 arms and control and demonstrated no T-20 dose-dependence. Observed Week 16 median log₁₀changes in pVL by arm were: A, -2.16; B, -2.20; C, -2.30; and D, -2.84. Corresponding CD4+ cell count changes were: A, +10; B, +37; C, +74; D, +64 cells/mm3. When using last observation carried forward, median change in pVL at Week 16 in the pooled T-20 treatment arms was -2.27 log₁₀compared to -1.65 in the control arm; for patients with baseline pVL >20,000 copies/mL, the differences were more marked (-2.64 for pooled T-20 arms versus -1.55 for control).

Conclusions:In patients failing prior therapy with at least one protease inhibitor and naïve to NNRTIs, the addition of T-20 to a standard antiretroviral regimen was well-tolerated and provided additional virologic and immunologic activity over and above that provided by the oral ARV regimen alone.