Program Schedule

540
HIV-1 Attachment Inhibitor Prodrug BMS-663068 in Antiretroviral-Experienced Subjects: Week 24 Subgroup Analysis

Session: Oral Abstract Session: HIV Antiretroviral Therapy
Thursday, October 9, 2014: 3:00 PM
Room: The Pennsylvania Convention Center: 107-AB
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/mm(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.

Cynthia Brinson1, Jacob Lalezari2, Gulam H Latiff3, Melanie Thompson, MD4, Juan Echevarría5, Sandra Treviño-Pérez6, David Stock7, Samit R Joshi7, George J Hanna8, Max Lataillade7 and AI438011 study team, (1)Central Texas Clinical Research, Austin, TX, (2)Quest Clinical Research, San Francisco, CA, (3)Maxwell Clinic, Durban, South Africa, (4)AIDS Research Consortium of Atlanta, Atlanta, GA, (5)Hospital Nacional Cayetano Heredia, Lima, Peru, (6)Mexico Centre for Clinical Research, Mexico City, Mexico, (7)Bristol-Myers Squibb, Wallingford, CT, (8)Bristol-Myers Squibb, Princeton, NJ

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

J. Lalezari, None

G. H. Latiff, None

M. Thompson, Bristol-Myers Squibb: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta only; no personal funding
Cepheid Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta only; no personal funding
Gilead Sciences, Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta only; no personal funding
GeoVax, Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta only; no personal funding
Kowa Research Institute: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta only; no personal funding
Pharmasset, Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta only; no personal funding
Pfizer, Inc.: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta only; no personal funding
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 only; no personal funding
Tobira Therapeutics: Grant Investigator, Research funding to conduct clinical trial to AIDS Research Consortium of Atlanta only; no personal funding
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

Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

Sponsoring Societies:

© 2014, idweek.org. All Rights Reserved.

Follow IDWeek