1347. Metabolic, Bone, Renal, Inflammatory, and Lipodystrophic Marker Analysis in INROADS, a Multicenter, Single-Arm, Open-Label Study of Once-Daily Etravirine (ETR) and Darunavir/Ritonavir (DRV/r) as Dual Therapy in Early Treatment-Experienced Subject
Session: Poster Abstract Session: Clinical Trials
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • 233TIBGRA130030-IDWeek2013-INROADS-BMD-Poster-v10DR.png (1.1 MB)
  • Background: Long-term toxicities of nucleoside/tide reverse transcriptase inhibitors include mitochondrial damage, lipodystrophy, bone loss, renal dysfunction and changes in lipid and glucose metabolism. The once daily (qd) nucleoside-sparing regimen of ritonavir boosted darunavir (DRV/r) combined with etravirine (ETR) may decrease toxicities while maintaining high virologic efficacy.

    Methods: INROADS (Intelence aNd pRezista Once A Day Study; NCT01199939) was a Phase 2, single-arm, 48-wk trial evaluating the efficacy and safety of ETR 400mg and DRV/r 800/100mg qd in HIV-1–infected patients (pts) who were early treatment-experienced (TE) or treatment-naïve with transmitted resistance (TNTR)., Metabolic, bone, renal, inflammatory and lipodystrophic markers were assessed through wk 48 (W48) via serum analysis and DEXA scanning.

    Results: 54 pts (78% male; 48% Black) were enrolled; 41 (76%) completed the study. Confirmed virologic response was seen in 89% of pts at W48 in a non-virologic failure censored analysis. 13 pts discontinued: 4 (7%) reached a virologic endpoint, 4 (7%) due to adverse events (AEs), 3 (6%) did not fulfill criteria and 2 (4%) were lost to follow-up. Grade 2-4 AEs were seen in 4 pts: increased LDL (n=1), hyperlipidemia (n=1) and rash (n=2).

    From baseline (BL) to W48, an increase in lipids, including LDL, HDL, total cholesterol (TC), triglycerides, apo A1 and apo B, were observed while TC:HDL ratio, insulin resistance (HOMA-IR) values, fasting glucose, insulin levels, and glomerular filtration rate remained relatively unchanged (Table).

    No clinically significant change in BMD was seen at W48. Risk of progression from insufficient (20 to <30ng/mL) and deficient (10 to <20ng/mL) to severely deficient (<10ng/mL) vitamin D levels from BL to W48 was 7% (2/27) pts. No significant changes in renal or inflammatory markers were seen.

    From BL to W48, 10 pts (29%) experienced greater than 20% loss of limb fat, and 10 pts (29%) experienced greater than 20% gain in trunk fat.

    Conclusion: ETR and DRV/r qd in TE or TNTR pts was virologically efficacious and well-tolerated, with mild/moderate lipid elevations and body fat redistribution. No clinically relevant changes in glucose metabolism, bone, renal function, and inflammation were observed.


    Moti N. Ramgopal, MD1, Fritz Bredeek, MD, PhD, FACP2, Joseph Gathe, MD3, Robert Ryan, MS4, Bruce Coate, BS, MPH4 and David Anderson5, (1)Midway Immunology and Research Center, Fort Pierce, FL, (2)Metropolis Medical, San Francisco, CA, (3)Therapeutic Concepts, Houston, TX, (4)Janssen Research & Development, Titusville, NJ, (5)Janssen Services, LLC, Titusville, NJ

    Disclosures:

    M. N. Ramgopal, None

    F. Bredeek, ViiV: Research Contractor, Scientific Advisor and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium
    Merck: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium
    Gilead: Research Contractor and Scientific Advisor, Consulting fee and Research grant
    Tibotec: Research Contractor, Research grant
    Kova: Research Contractor, Research grant

    J. Gathe, Therapeutic Concepts: Investigator, Research grant

    R. Ryan, Janssen Research & Development: Employee and Shareholder, Salary

    B. Coate, Janssen Research & Development: Independent Contractor, Salary

    D. Anderson, Janssen Services, LLC: Employee and Shareholder, Salary

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