1075. HIV-1 Attachment Inhibitor Prodrug BMS-663068 in Antiretroviral-Experienced Subjects: Week 48 Subgroup Analysis
Session: Poster Abstract Session: HIV: New Antiretrovirals
Friday, October 9, 2015
Room: Poster Hall
Posters
  • Feinberg et al_IDWeek 2015_AI Week48 Subgroup Analysis_ePoster.pdf (519.8 kB)
  • 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 an ongoing Phase IIb, randomized, controlled trial investigating the safety, efficacy and dose–response of BMS-663068 versus atazanavir/ritonavir (ATV/r), both given with raltegravir (RAL)+ tenofovir disoproxil fumarate (TDF), in treatment-experienced (TE), HIV-1-infected subjects. Through 48 weeks, BMS-663068 showed similar efficacy to ATV/r. We present here a subgroup analysis of viral efficacy and immunologic response through Week 48.

                                         

    Methods:

    TE subjects (exposure to ≥1 antiretroviral for ≥1 week) with susceptibility to all study drugs and BMS-626529 IC50 <100 nM, were randomized equally to receive BMS-663068 (400 or 800 mg BID; 600 or 1200 mg QD) or ATV/r 300/100 mg QD, both given with RAL + TDF. The study was not powered to detect statistically significant differences between subgroups.

     

    Results:

    251 subjects 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 230 cells/mm3 (38% <200 CD4 cells/mm3). At Week 48, response rates (HIV-1 RNA <50 c/mL) were generally similar across the BMS-663068 arms and the ATV/r arm regardless of gender, age and race (Table). For the BMS-663068 arms and the ATV/r arm, response rates were generally higher in subjects with BL VL <100,000 c/mL and in those with BL CD4+ T-cell counts ≥200 cells/mm3, however the differences were not substantial. Mean increases in CD4+ T-cell count from BL to Week 48 were similar in the BMS-663068 arms regardless of age, gender, race, and BL CD4+ T-cell count.

    Conclusion:

    At Week 48, virologic response was generally similar across the BMS-663068 arms and the ATV/r arm in TE subjects, regardless of gender, race, age, BL VL, or BL CD4+ T-cell count. Mean increases in CD4+ T-cell count from BL to Week 48 were similar in the BMS-663068 arms regardless of age, gender, race, and BL CD4+ T-cell count. These results are mostly in agreement with those reported at Week 24 and support the ongoing Phase III trial evaluating BMS-663068 for use in heavily treatment-experienced adults with limited therapeutic options (NCT02362503).

               

    Judith Feinberg, MD1, Jacob Lalezari, MD2, Marcelo Martins, MD3, Martin Casapia, MD, MPH4, David Stock, PhD5, Cyril Llamoso, MD5, Samit Joshi, DO MPH5, George Hanna, MD6, Max Lataillade, DO MPH5 and the AI438011 study team, (1)University of Cincinnati, Cincinnati, OH, (2)Quest Clinical Research, San Francisco, CA, (3)Instituto Oulton, Córdoba, Argentina, (4)Asociación Civil Selva Amazónica, Iquitos, Peru, (5)Bristol-Myers Squibb, Wallingford, CT, (6)Bristol-Myers Squibb, Princeton, NJ

    Disclosures:

    J. Feinberg, Bristol-Myers Squibb: Consultant and Grant Investigator , Grant recipient and Speaker honorarium
    ViiV/GlaxoSmithKline: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Grant recipient and Speaker honorarium
    Gilead Sciences: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Grant recipient and Speaker honorarium
    Merck: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Grant recipient and Speaker honorarium
    Hamilton County Public Defense Office: Expert testimony , Paid an hourly rate for expert testimony
    Tobira Therapeutics: Grant Investigator , Grant recipient
    Janssen: Grant Investigator , Grant recipient
    Bristol-Myers Squibb: Consultant , Supprt for travel to meetings for the study or other purposes
    ViiV/GlaxoSmithKline: Payment for development of educational presentations , Consulting fee
    Merck: Payment for development of educational presentations , Consulting fee
    Gilead Sciences: Payment for development of educational presentations , Consulting fee
    HIV medical association: Board Member , Travel to board meetings paid

    J. Lalezari, Bristol-Myers Squibb: Grant Investigator , Research support

    M. Martins, None

    M. Casapia, None

    D. Stock, Bristol-Myers Squibb: Employee and Shareholder , Salary

    C. Llamoso, Bristol-Myers Squibb: Employee and Shareholder , Salary

    S. Joshi, Bristol-Myers Squibb: Employee and Shareholder , Salary

    G. Hanna, Bristol-Myers Squibb: Employee and Shareholder , Salary

    M. Lataillade, Bristol-Myers Squibb: Employee and Shareholder , Salary

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