7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013)


WEPE512 - Poster Exhibition

RADAR study: week 48 safety and efficacy of raltegravir combined with boosted darunavir compared to tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naive patients. Impact on bone health

R. Bedimo1,2, H. Drechsler1,2, J. Cutrell2, M. Jain2, P. Tebas3, N. Maalouf2

1VA North Texas Health Care System, Medicine, Dallas, United States, 2UT Southwestern Medical Center, Medicine, Dallas, United States, 3University of Pennsylvania, Medicine, Philadelphia, United States

Background: All currently preferred regimens for antiretroviral-naive patients include two nucleoside reverse transcriptase inhibitors (NRTIs). NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression. RADAR was a randomized, open label, 48-week pilot study comparing Raltegravir (RAL) and Tenofovir/Emtri¬≠citabine (TDF/FTC), in combination with Ritonavir-boosted Darunavir (DRV/r) in antiretroviral-naive subjects with HIV-1 RNA ≥ 5,000 copies/mL.
Methods: Eighty-five patients were randomized to receive either RAL 400 mg BID (n=42) or TDF/FTC 300/200 mg QD (n=43), with DRV/r 800/100 mg QD. Subjects underwent bone mineral density (BMD) testing by DXA scan and measurement of fasting bone turnover markers (BTM) at baseline, week 16 and week 48: Serum C-telopeptide (CTx) for bone resorption and Procollagen type 1 N-terminal propeptide (P1NP) for bone formation.
Results: Using the mITT (Non-complete = failure) analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL < 48 copies/mL) at week 48 (p=0.045; chi-square test). The proportions of patients achieving VL< 200 copies/mL were similar: 72.5% and 86.0% respectively (p=0.175). Premature treatment discontinuation - 8 (19.0%) of RAL subjects and 6 (14.0%) of TDF/FTC subjects - was the main cause for failure. No treatment-emergent resistance was observed. Only two patients in RAL and 0 in TDF/FTC had VL >200 copies/mL at the time of discontinuation.
Changes from baseline for CD4+ T-cells (+199 in RAL vs. +216 in TDF/FTC, p=0.63), mean LDL (+17% vs. +12%, p=0.7), and mean eGFR (-4.4 vs. -7.9, p=0.44) were comparable between groups but changes in subtotal BMD differed significantly (+1.02% vs. -0.76%, p=0.002). CTx and P1NP increased significantly in the TDF/FTC group (+112%, resp. +85%, p=0.01 for both), but not in the RAL group (+20%, p=0.22; and +11%, p=0.33). Week 16 changes in BTM predicted week 48 changes in BMD (R= -0.394, p=0.003 for CTx; and R= -0.477, p< 0.001 for P1NP).
Conclusion: The NRTI-sparing regimen RAL + DRV/RTV did not achieve similar week 48 virologic efficacy compared with TDF/FTC + DRV/r but was better with regard to markers of bone health. In antiretroviral therapy naive patients, NRTI-sparing regimens may be associated with less bone loss.

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