405. Raltegravir (RAL)-based Therapy Demonstrates Superior Virologic Suppression and Immunologic Response Compared with Efavirenz (EFV)-based Therapy, with a Favorable Metabolic Profile Through 4 Years in Treatment-naïve Patients: 192 Week (Wk) Results from STARTMRK
Session: Poster Abstract Session: HIV - Antiretroviral Therapy
Friday, October 21, 2011
Room: Poster Hall B1
Handouts
  • IDSA2011_P021wk192_FINAL.pdf (641.4 kB)
  • Background: As the paradigm of HIV treatment has evolved to lifelong therapy with greater relevance of co-morbidities, long-term efficacy and safety data are essential to distinguish regimens. We now report 192 wk results from STARTMRK, a Phase III study of RAL- vs efavirenz (EFV)-based therapy in treatment (tx)-naïve patients.

     

    Methods: 563 patients were randomized to RAL or EFV, both with tenofovir/emtricitabine (TDF/FTC), in a double-blind study comparing standard efficacy endpoints and metabolic parameters. Primary analysis was at Wk 48 and secondary analysis at Wk 96. Standard efficacy endpoints were analyzed at Wk 192. Nominal p-values and 95% CI are reported.

     

    Results:

     

    % (n/N) of Patients with HIV RNA <50 copies/mL

    Change from BL in CD4 Cell Count (cells/mm3) ††

    Week

    RAL (N=281)

    EFV (N=282)

    RAL - EFV†

    RAL (N=281)

    EFV (N=282)

    RAL - EFV†

    48

    86.1 (241/280)

    81.9  (230/281)

    4.2* (-1.9, 10.3)

    189.1

    163.3

    25.8 (4.4, 47.2)

    96

    81.1  (228/281)

    78.7  (222/282)

    2.4* (-4.3, 9.0)

    240.1

    224.8

    15.2 (-12.2, 42.6)

    156

    75.4  (212/281)

    68.8  (194/282)

    6.6* (-0.8, 14.0)

    331.3

    295.4

    35.9 (3.4, 68.3)

    192

    76.2 (214/281)

    67.0 (189/282)

    9.0* (1.6, 16.4)

    360.7

    300.9

    59.8 (24.1, 95.4)

    ‡ Non-Completer=Failure (NC=F): Patients who discontinued tx regardless of reasons were considered as failures thereafter.

    †† Observed Failure (OF): Patients who discontinued tx due to lack of efficacy were considered as failures thereafter; BL values carried forward for virologic failures.

    †Difference between RAL and EFV (95%CI)

    µ RAL would be considered non-inferior to EFV if the lower bound of the 95% CI for the difference in % response was above -12%, and superior to EFV if the lower bound exceeds 0.

    *p-value for non-inferiority <0.001

    Drug-related clinical adverse events (AEs) occurred less often with RAL than EFV (50% vs 80%; p<0.001). RAL was generally well tolerated with few discontinuations due to clinical AEs (5% RAL, 8% EFV). At Wk 192, RAL had less impact on fasting lipids than EFV.

    Conclusion: After 4 years of treatment, RAL + TDF/FTC is associated with superior antiretroviral efficacy and CD4 responses vs. EFV + TDF/FTC in treatment-naïve patients.  The long-term tolerability and metabolic profile of this integrase-based regimen appear favorable.


    Subject Category: H. HIV/AIDS and other retroviruses

    Edwin DeJesus, MD, FACP1, Jurgen Rockstroh2, Jeffrey Lennox, MD3, Michael S. Saag, MD, FIDSA4, Adriano Lazzarin5, Hong Wan6, Anthony Rodgers6, Kim Strohmaier6, Hedy Teppler, MD6, Bach-Yen Nguyen6, Randi Leavitt6 and Peter Sklar6, (1)Orlando Immunology Center, Orlando, FL, (2)Univ of Bonn, Venusburg, Germany, (3)Emory University School of Medicine, Atlanta, GA, (4)Univ. of Alabama, Birmingham, AL, (5)San Raffaele Hospital, Milan, Italy, (6)Merck, Upper Gwynedd, PA

    Disclosures:

    E. DeJesus, Merck: Consultant and Speaker's Bureau, Research support and Speaker honorarium
    Bristol-Myers Squibb: Consultant and Speaker's Bureau, Research support and Speaker honorarium
    Gilead Sciences: Consultant and Speaker's Bureau, Research support and Speaker honorarium
    GlaxoSmithKline: Investigator and Speaker's Bureau, Research support and Speaker honorarium
    Tibotec: Investigator and Speaker's Bureau, Research support and Speaker honorarium
    Pfizer: Research support - No grant, Research support
    Hoffman LaRoche: Research support - No grant, Research support
    Achillion: Research support - No grant, Research support
    Avexa: Research support - No grant, Research support
    Taimed: Research support - No grant, Research support

    J. Rockstroh, Merck: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    Abbott: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    BMS: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    Boehringer: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    Ingelheim: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    Gilead: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    GSK: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    Pfizer: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    Roche: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    Tibotec: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium
    ViiV: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium

    J. Lennox, Merck: Consultant, Consulting fee

    M. S. Saag, Merck: Consultant and Scientific Advisor, Consulting fee
    Ardea: Consultant and Scientific Advisor, Consulting fee
    Boehringer: Consultant and Scientific Advisor, Consulting fee
    Ingelheim: Consultant and Scientific Advisor, Consulting fee
    BMS: Consultant and Scientific Advisor, Consulting fee
    Gilead: Consultant and Scientific Advisor, Consulting fee
    GSK: Consultant and Scientific Advisor, Consulting fee
    Pfizer: Consultant and Scientific Advisor, Consulting fee
    VIiV: Consultant and Scientific Advisor, Consulting fee
    Tibotec: Consultant and Scientific Advisor, Consulting fee
    Vertex: Scientific Advisor, Consulting fee
    Monogram BioSciences: Research Contractor, Research support
    NIH/NIAID: Grant Investigator, Grant recipient

    A. Lazzarin, Merck: Board Member, Consultant, Grant Investigator, Investigator, Research Contractor, Scientific Advisor and Speaker's Bureau, Consulting fee, Educational grant, Educational support, Grant recipient, Research grant, Research support and Speaker honorarium
    BMS: Board Member, Consultant, Grant Investigator, Investigator, Research Contractor, Scientific Advisor and Speaker's Bureau, Consulting fee, Educational grant, Educational support, Grant recipient, Research grant, Salary and Speaker honorarium
    ViiV: Board Member, Consultant, Grant Investigator, Research Contractor, Scientific Advisor and Speaker's Bureau, Consulting fee, Educational grant, Educational support, Grant recipient, Research grant and Speaker honorarium
    Roche: Board Member, Consultant, Grant Investigator, Research Contractor, Scientific Advisor and Speaker's Bureau, Consulting fee, Educational grant, Educational support, Grant recipient, Research grant and Speaker honorarium
    Gilead: Board Member, Consultant, Grant Investigator, Investigator, Research Contractor and Scientific Advisor, Consulting fee, Educational grant, Educational support, Grant recipient, Research grant and Speaker honorarium
    Abbott: Board Member, Consultant, Grant Investigator, Research Contractor, Scientific Advisor and Speaker's Bureau, Consulting fee, Educational grant, Educational support, Grant recipient, Research grant and Speaker honorarium

    H. Wan, Merck: Employee, Salary

    A. Rodgers, Merck: Employee, Company stock options and Salary

    K. Strohmaier, Merck: Employee, Salary

    H. Teppler, Merck: Employee, Salary and Stock Options

    B. Y. Nguyen, Merck: Employee, Salary and Stock Options

    R. Leavitt, Merck: Employee, Salary

    P. Sklar, Merck: Employee, Salary and Stock Options

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.