A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy–induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial
| Autor: | M. Neale Weitzmann, Anandi N. Sheth, Kehmia Titanji, Philip Powers, Sara E. Sanford, Cecile D. Lahiri, Laura Ward, Antonina Foster, Aswani Vunnava, Jeffrey L. Lennox, Andrea Knezevic, Kirk A. Easley, Ighovwerha Ofotokun |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Microbiology (medical) medicine.medical_specialty Urology HIV Infections Emtricitabine Zoledronic Acid Bone resorption Bone remodeling 03 medical and health sciences 0302 clinical medicine N-terminal telopeptide medicine Humans 030212 general & internal medicine Bone mineral Bone Density Conservation Agents Diphosphonates business.industry Imidazoles Middle Aged medicine.disease Surgery Osteopenia 030104 developmental biology Infectious Diseases Zoledronic acid Anti-Retroviral Agents HIV/AIDS Osteoporosis RNA Viral Female Ritonavir business medicine.drug |
| Zdroj: | Clinical Infectious Diseases. 63:663-671 |
| ISSN: | 1537-6591 1058-4838 |
| DOI: | 10.1093/cid/ciw331 |
| Popis: | BACKGROUND Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among HIV-infected individuals. ART-induced bone loss is most intense within the first 48 weeks of therapy, providing a window for prophylaxis with long-acting antiresorptives. METHODS In a phase 2, double-blind, placebo-controlled trial, we randomized 63 nonosteoporotic, ART-naive adults with HIV initiating ART with atazanavir/ritonavir + tenofovir/emtricitabine to a single zoledronic acid (ZOL) infusion (5 mg) vs placebo to determine the efficacy of ZOL in mitigating ART-induced bone loss. Plasma bone turnover markers and bone mineral density (BMD) were performed at weeks 0, 12, 24, and 48 weeks. Primary outcome was change in C-terminal telopeptide of collagen at 24 weeks. Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. RESULTS The ZOL arm had a 65% reduction in bone resorption relative to the placebo arm at 24 weeks (0.117 ng/mL vs 0.338 ng/mL; P < .001). This effect of ZOL occurred as early as 12 weeks (73% reduction; P < .001) and persisted through week 48 (57% reduction; P < .001). The ZOL arm had an 8% higher lumbar spine BMD at 12 weeks relative to the placebo arm (P = .003), and remained 11% higher at 24 and 48 weeks. Similar trends were observed in the hip and femoral neck. CONCLUSIONS A single dose of ZOL administered at ART initiation prevented ART-induced bone loss through the first 48 weeks of ART, the period when ART-induced bone loss is most pronounced. Validation of these results in larger multicenter randomized clinical trials is warranted. CLINICAL TRIALS REGISTRATION NCT01228318. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|