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

• Published in: PloS one Vol. 9; no. 8; p. e106221
• Main Authors: Bedimo, Roger J., Drechsler, Henning, Jain, Mamta, Cutrell, James, Zhang, Song, Li, Xilong, Farukhi, Irfan, Castanon, Rosinda, Tebas, Pablo, Maalouf, Naim M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.08.2014; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adenine - administration & dosage; Adenine - analogs & derivatives; Adult; AIDS; Antiretroviral agents; Antiretroviral drugs; Biology and Life Sciences; Bone (long); Bone density; Bone Density - drug effects; Bone mineral density; Bone turnover; CD4 antigen; Chi-square test; Cholesterol; Collagen; Darunavir; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Dual energy X-ray absorptiometry; Effectiveness; Emtricitabine; Epidermal growth factor receptors; High density lipoprotein; HIV; HIV Infections - drug therapy; HIV Infections - metabolism; HIV Infections - pathology; HIV-1; Human immunodeficiency virus; Humans; Lipoproteins (high density); Long bone; Markers; Medicine and health sciences; Middle Aged; Mitochondria; Motivation; Organophosphonates - administration & dosage; Patients; Pyrrolidinones - administration & dosage; Radar; Raltegravir Potassium; Ritonavir; Statistical tests; Sulfonamides - administration & dosage; Tenofovir; Toxicity; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106221

NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression. 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. 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). 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. ClinicalTrials.gov NCT 00677300.