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

AIDS. 2018 Sep 10;32(14):1967-1975. 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Aged
  • Anti-HIV Agents / administration & dosage*
  • Australia
  • Bone Density
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Diseases, Metabolic / prevention & control*
  • Drug Substitution*
  • Female
  • Femur Neck / diagnostic imaging
  • HIV Infections / complications*
  • Humans
  • Lumbar Vertebrae / diagnostic imaging
  • Male
  • Middle Aged
  • Spain
  • Tenofovir / administration & dosage*
  • Treatment Outcome
  • Viral Load
  • Zoledronic Acid / administration & dosage*


  • Anti-HIV Agents
  • Bone Density Conservation Agents
  • Zoledronic Acid
  • Tenofovir