Session: Slide Session: Antiretroviral Therapy
Sunday, October 26, 2008: 12:00 AM
Room: Independence A (Grand Hyatt)
Background: BVM is a novel HIV-1 maturation inhibitor targeting the Gag capsid SP-1 cleavage site. A prior 10 day study showed a 1 log viral load reduction (VLR) in patients given BVM 200mg QD. A separate retrospective analysis showed that patients without key baseline Gag polymorphisms at Q369, V370 or T371 were more likely to respond to BVM. Methods: In a Phase 2 double-blind, randomized dose escalation study, 59 treatment-experienced patients with >1 primary resistance mutation received 2 weeks of BVM or placebo as functional monotherapy on top of a failing (VL >2000 copies/mL) background regimen. Patients initially received a 400mg BVM tablet dose, or placebo; in the modified study, patients received a 250, 300, 350 or 400mg BVM liquid dose, or placebo. Results: Of 44 patients given the assigned BVM dose, the mean VL change was -0.6 log copies/mL (+0.05 log for 13 patients given placebo); 12/13 (92%) patients with BVM trough levels >20 ug/mL and without the key Gag polymorphisms had a VLR >0.5 log; 10/13 (77%) had a VLR >1.0 log (group mean VLR: -1.26 log). 32/46 (70%) BVM treated patients and 10/13 (77%) placebo treated patients had >1 adverse event (AE). For BVM and placebo treated patients respectively, the most common AEs were diarrhea (22%; 39%), nausea (20%; 31%) and headache (20%; 23%); all were Grade 1. For BVM and placebo treated patients respectively, the most common lab changes were: glucose (13%; 8%), total cholesterol (11%, 15%) and triglycerides (9%, 15%); nearly all were Grade 2. Conclusion: Through 2 weeks BVM and placebo were similarly well tolerated, and responder patients with BVM troughs >20 ug/mL had a high magnitude VLR of 1.26 log. Planned Phase 3 studies will employ these criteria to confirm the utility of BVM in treatment-experienced patients.