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Zoledronic acid is superior to tenofovir disoproxil fumarate-switching for low bone mineral density in adults with HIV

Hoy, Jennifer F.a; Richardson, Robynb; Ebeling, Peter R.c; Rojas, Jhond; Pocock, Nicholasb; Kerr, Stephen J.b,e; Martinez, Esteband; Carr, Andrewb for the ZEST Study Investigators

doi: 10.1097/QAD.0000000000001911

Objective: To compare the effects of switching tenofovir disoproxil fumarate (TDF) or treatment with an intravenous bisphosphonate on bone mineral density (BMD) in HIV-positive adults with low bone mass.

Design: Two-year, randomized, open-label study at 10 sites in Australia and Spain.

Participants: Of 112 adults on TDF-based antiretroviral therapy (ART) screened, 87 with low BMD (T-score < −1.0 at hip or spine by dual-energy X-ray absorptiometry) and undetectable plasma HIV viral load were randomized to either switch TDF to another active antiretroviral drug or to continue TDF-based ART and receive intravenous zoledronic acid (ZOL) 5 mg annually for 2 years.

Primary outcome measure: Change in lumbar spine BMD at 24 months by intention-to-treat analysis. Secondary outcomes included changes in femoral neck and total hip BMD, fractures, safety, and virological failure.

Results: Forty-four participants were randomized to TDF switch and 43 to ZOL, mean age 50 years (SD 11), 96% men, mean TDF duration 5.9 years (SD 3.1), and mean spine and hip T-scores −1.6 and −1.3, respectively. At 24 months, mean spine BMD increased by 7.4% (SD 4.3%) with ZOL vs. 2.9% (SD 4.5%) with TDF-switch (mean difference 4.4%, 95% CI 2.6–6.3; P < 0.001). Mean total hip BMD increased by 4.6 (SD 2.6%) and 2.6% (SD 4%), respectively (mean difference 1.9%, 95% CI 0.5–3.4; P = 0.009). There was one fracture in the ZOL group vs. seven fractures in four TDF-switch participants. Virological failure occurred in one TDF-switch participant. Other safety endpoints were similar.

Conclusion: ZOL is more effective than switching TDF at increasing BMD in HIV-positive adults with low bone mass.

aAlfred Hospital and Monash University, Melbourne

bSt Vincent's Hospital, Sydney

cMonash University, Melbourne, Australia

dHospital Clinic, University of Barcelona, Barcelona, Spain

eFaculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Correspondence to Jennifer F. Hoy, MBBS, FRACP, Director, HIV Medicine, Department of Infectious Diseases, The Alfred Hospital and Monash University, 85 Commercial Road, Melbourne, VIC 3004, Australia. E-mail:

Received 29 January, 2018

Revised 19 May, 2018

Accepted 22 May, 2018

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Copyright © 2018 Wolters Kluwer Health, Inc.