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

Jennifer F. Hoy, Robyn Richardson, Peter R. Ebeling, Jhon Rojas, Nicholas Pocock, Stephen J. Kerr, Esteban Martinez, Andrew Carr, for the ZEST Study Investigators

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18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1967-1975
Number of pages9
Issue number14
Publication statusPublished - 10 Sept 2018

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