Background. 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 (sbj).
Methods. Antiretroviral TE sbj (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 subgroup analysis of viral efficacy and immunologic reconstitution is presented.
Results. 251 sbj were treated. Median age was 39 years, 60% were male and 38% 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 sbj with BL VL <100,000 c/mL (BMS-663068, 82–96%; ATV/r, 93%) were higher than those for sbj 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 subgroup. Response rates for sbj with BL CD4+ cell counts ≥200 cells/mm3 (87–96%) were higher than those for sbj 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 subgroup. 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.
Disclosures. C. Brinson, Bristol-Myers Squibb: Investigator, Central Texas Clinical Research received monies for conducting the trial; Gilead: Board Member and Speaker, sit on advisory board, sit on education board, personal fees; Boehringer Ingelheim: Investigator, Contract Principal Investigator for clinical trials; Bristol-Myers Squibb: Investigator, Contract Principal Investigator for clinical trials; ViiV: Investigator, Contract Principal Investigator for clinical trials; GlaxoSmithKline: Investigator, Contract Principal Investigator for clinical trials; Gilead: Investigator, Contract Principal Investigator for clinical trials; Shionogi: Investigator, Contract Principal Investigator for clinical trials; AstraZeneca: Investigator, Contract Principal Investigator for clinical trials; Pfizer: Investigator, Contract Principal Investigator for clinical trials; Janssen: Investigator, Contract Principal Investigator for clinical trials; Sangamo: Investigator, Contract Principal Investigator for clinical trials; Taimed: Investigator, Contract Principal Investigator for clinical trials; Theratechnologies: Investigator, Contract Principal Investigator for clinical trials; Serono: Investigator, Contract Principal Investigator for clinical trials; Achillion: Investigator, Contract Principal Investigator for clinical trials M. Thompson, Bristol-Myers Squibb: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; Cepheid Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; Gilead Sciences, Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; GeoVax, Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; Kowa Research Institute: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; Pharmasset, Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; Pfizer, Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; Janssen/Tibotec Therapeutics: Grant Investigator, Grant recipient and Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; honorarium for DSMB; Merck & Co.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; Tobira Therapeutics: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; ViiV Healthcare: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta; honorarium for DSMB; J. Echevarría, Bristol-Myers Squibb: Grant Investigator, Grant recipient S. Treviño-Pérez, Bristol-Myers Squibb: Grant Investigator, Grant recipient D. Stock, Bristol-Myers Squibb: Employee and Shareholder, Salary S. R. Joshi, Bristol-Myers Squibb: Employee and Shareholder, Salary G. J. Hanna, Bristol-Myers Squibb: Employee and Shareholder, Salary M. Lataillade, Bristol-Myers Squibb: Employee and Shareholder, Salary