title: The 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.
abstract: BACKGROUND
  NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression.
  
  
  METHODS
  In the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) scan at baseline and week 48, and bone turnover markers (BTM) assessed at weeks 0, 16 and 48.
  
  
  RESULTS
  Using an intention-to-treat 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% (p = 0.175). Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4+ (+199 vs. +216 cells/µL, p = 0.63), total cholesterol/HDL (-0.25 vs. -0.71 mg/dL (p = 0.270), and eGFR (-4.4 vs. -7.9 ml/min, p = 0.44) were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. -7 g/cm2 with TDF/FTC (p = 0.002). Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001), and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023). BTM changes at week 16 predicted change in BMD by week 48 (R = -0.394, p = 0.003 for CTX; and R = -0.477, p<0.001 for P1NP).
  
  
  CONCLUSIONS
  The NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT 00677300.
authors.affiliation: Department of Medicine, VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Bedimo
authors.affiliation: Department of Medicine, VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Henning
authors.initials: H
authors.lastname: Drechsler
authors.affiliation: Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Mamta
authors.initials: M
authors.lastname: Jain
authors.affiliation: Department of Medicine, VA North Texas Health Care System, Dallas, Texas, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Cutrell
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Xilong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, VA North Texas Health Care System, Dallas, Texas, United States of America.
authors.forename: Irfan
authors.initials: I
authors.lastname: Farukhi
authors.affiliation: Department of Nuclear Medicine, VA North Texas Health Care System, Dallas, Texas, United States of America.
authors.forename: Rosinda
authors.initials: R
authors.lastname: Castanon
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.affiliation: Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Naim M
authors.initials: NM
authors.lastname: Maalouf
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D000069454:Darunavir; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068679:Emtricitabine; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015497:HIV-1; D006801:Humans; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D011760:Pyrrolidinones / Q000008:administration & dosage*; D000068898:Raltegravir Potassium; D013449:Sulfonamides / Q000008:administration & dosage*; D000068698:Tenofovir
chemical_list: D063065:Organophosphonates; D011760:Pyrrolidinones; D013449:Sulfonamides; D003841:Deoxycytidine; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D000069454:Darunavir