Abstract
INTRODUCTION: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into the host CD4+ T-cell. AI438011 is a Phase IIb, randomized, active-controlled trial investigating the safety, efficacy and dose-response of BMS-663068 versus atazanavir/ritonavir (ATV/r) in treatment-experienced (TE), HIV-1-positive subjects. MATERIALS AND METHODS: Antiretroviral TE subjects (exposure to ≥1 antiretroviral for ≥1 week) with susceptibility to all study drugs (BMS-626529 IC50 100 nM), were randomized equally to four BMS-663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD) and a control group (ATV/r 300/100 mg QD) with tenofovir disoproxil fumarate (TDF) + raltegravir (RAL). A sub-group analysis of viral efficacy and immunologic reconstitution is presented. RESULTS: A total of 251 subjects were treated. Median age was 39 years, 60% were male and 38% were white. Median baseline (BL) viral load (VL) was 4.85 log10 c/mL (43%; 100,000 c/mL) and median CD4+ T-cell count was 230 cells/mm(3) (38%; 200 CD4 cells/mm(3)). Through Week 24, response rates (HIV-1 RNA 50 c/mL) were comparable across all BMS-663068 arms and the ATV/r arm regardless of gender, age and race. Response rates for subjects with BL VL 100,000 c/mL (BMS-663068, 82-96%; ATV/r, 93%) were higher than those for subjects with BL VL ≥100,000 c/mL (BMS-663068, 70-87%; ATV/r, 73%); however, there were no substantial differences in response across the BMS-663068 and ATV/r arms in either sub-group. Response rates for subjects with BL CD4+ cell counts ≥200 cells/mm(3) (87-96%) were higher than those for subjects with BL CD4+ cell counts 200 cells/mm(3) (62-82%); however, no substantial differences in response were seen across the BMS-663068 and ATV/r arms in either sub-group. Mean changes in CD4+ T-cell counts from BL were similar across all arms regardless of gender, age and BL CD4+ T-cell count. CONCLUSION: Virologic response rates were similar across the BMS-663068 and ATV/r arms in TE subjects, regardless of BL demographic characteristics (gender, race, age), BL HIV-1 RNA, or BL CD4+ T-cell count. Mean increases in CD4+ T-cell counts across the BMS-663068 arms were consistent with ATV/r, regardless of gender, age and BL CD4+ T-cell count. These results support continued development of BMS-663068. Note: Previously submitted at IDWeek, Philadelphia, PA, 8 October 2014.