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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT 00677300.

Trial registration: ClinicalTrials.gov NCT00677300.

Conflict of interest statement

Competing Interests: Roger Bedimo has received research grants from Merck & Co, Janssen Therapeutics, and Bristol Myers Squibb. He’s also on ad-hoc scientific advisory boards for Janssen Therapeutics, ViiV Health Care, and Bristol Myers Squibb. Pablo Tebas is consultant for Merck & Co. and Gilead, speaker for Janssen Therapeutics and is on the adjudication committee for GSK. This specific study was funded by grants from Merck & Co, and Janssen Therapeutics to the VA North Texas Health Care System for Roger Bedimo. Raltegravir is a drug produced by Merck & Co. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1. CONSORT Flow Diagram.

Figure 2. Proportion of subjects with plasma HIV-1 RNA

Figure 3. Changes in bone turnover markers from baseline to week 48 (number of patients indicated).

Top: Serum Terminal Telopeptide (CTX). †p

Figure 4. Correlation between early changes in bone turnover markers (week 16 vs. week 0) and change in BMD by week 48.

Figure 4A: Correlation for serum P1NP. Figure 4B: Correlation for serum CTX.