HIV‐1 attachment inhibitor prodrug BMS‐663068 in antiretroviral‐experienced subjects: week 24 sub‐group analysis

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/mm3 (38%; 200 CD4 cells/mm3). 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/mm3 (87‐96%) were higher than those for subjects with BL CD4+ cell counts 200 cells/mm3 (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.