Drug Safety

, Volume 39, Issue 3, pp 209–218 | Cite as

Renal and Bone Adverse Effects of a Tenofovir-Based Regimen in the Treatment of HIV-Infected Children: A Systematic Review

  • Rose I. Okonkwo
  • Anita E. Weidmann
  • Emmanuel E. Effa
Systematic Review



Tenofovir disoproxil fumarate (TDF)-containing regimens in the treatment of HIV-infected children have safety concerns with respect to renal and bone toxicity.


The aim of this study was to systematically review and critically appraise the literature relating to the reported renal and bone adverse effects of TDF-based regimens in the treatment of HIV-infected children from 2 to 19 years old.


Searches were performed using the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, OvidSP, ScienceDirect and Web of Science databases and platforms. All primary studies involving tenofovir use in HIV-infected children were sought. Studies that involved the use of TDF for pre- and post-exposure prophylaxis, and treatment of chronic hepatitis B virus infection were excluded. Data on study characteristics, participant’s characteristics, therapeutic intervention and adverse effects were extracted using a piloted tool. In addition, pharmacovigilance data from the WHO Adverse Reaction database were included.


We identified 19 studies that reported the presence of renal and bone adverse effects of TDF and these included a total of 1100 study participants. The reports were in distinctly heterogeneous participant groups. A total of 287 renal and bone adverse effects were reported (250 renal and 37 bone adverse effects). Approximately 238 (21.6 %) participants were affected by these adverse effects. Of these, 15 participants stopped their TDF-containing regimen due to these adverse effects. In addition, the pharmacovigilance data from the WHO Adverse Reaction database reported 101 renal and bone adverse effects for patients whose indication was HIV/AIDS.


This systematic review summarises the reports of renal and bone adverse effects of a TDF-containing regimen in the treatment of HIV-infected children. Our findings suggest that the benefits of using TDF in children need to be balanced against the potential risk of toxicity.


Bone Mineral Density Tenofovir Electronic Supplementary Material Table Tenofovir Disoproxil Fumarate Fanconi Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to thank Mr. Ekpereonne Esu for his timely help in literature search strategies and study selection process and Dr. Christopher Akolo for retrieval of some full-text studies.

Compliance with Ethical Standards


No sources of funding were used to assist in the preparation of this study.

Conflicts of interest

Rose Okonkwo, Anita Weidmann and Emmanuel Effa have no conflicts of interest that are directly relevant to the content of this study.

Supplementary material

40264_2015_371_MOESM1_ESM.pdf (216 kb)
Supplementary material 1 (PDF 216 kb)


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Rose I. Okonkwo
    • 1
  • Anita E. Weidmann
    • 2
  • Emmanuel E. Effa
    • 3
  1. 1.Department of Child HealthUniversity of Benin Teaching HospitalBenin CityNigeria
  2. 2.School of Pharmacy, Faculty of Health and Social CareRobert Gordon UniversityAberdeenUK
  3. 3.Internal Medicine, Faculty of Medicine and DentistryUniversity of CalabarCalabarNigeria

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