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Tenofovir-Associated Nephrotoxicity in Children with Perinatally-Acquired HIV Infection: A Single-Centre Cohort Study

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Abstract

Background and Objective

In 2012, tenofovir disoproxil fumarate (TDF) was approved for use in children over 2 years of age at a dose of 8 mg/kg/day, and is the WHO recommended first-line therapy for children over 10 years of age or 35 kg in weight, at 300 mg daily. Whilst postmarketing experience of paediatric TDF is limited, prior off-licence use has occurred at our centre due to its tolerability, efficacy and resistance profiles. In this article we describe a single-centre experience of TDF nephrotoxicity in children aged <16 years.

Methods

We conducted a retrospective case-note audit of children with perinatally-acquired HIV who ever received TDF-based antiretroviral therapy.

Results

From 2001 to December 2013, 70 children [39 (56 %) females] ever received TDF. Median age at the start of TDF treatment was 12 years (interquartile range 10–14). Seven (10 %) children developed asymptomatic renal tubular leak with associated hypophosphataemia (3) and hypokalaemia (1), all resulting in TDF withdrawal and biochemical resolution. Comparison of the nephrotoxic group versus the rest of the cohort showed no significant differences for age, sex, antiretroviral regimen or CD4 count. Lower weight (p = 0.05) and initial dose of TDF received (p = 0.0048) were significantly associated with TDF-induced nephrotoxicity: median dose of TDF (7.8 mg/kg/day) compared with the remainder of the cohort (6.5 mg/kg/day). Concurrent use of protease inhibitors (PIs) with TDF may be a contributing factor to the development of nephrotoxicity (odds ratio 6; 95 % CI 0.7–54; p = 0.111).

Conclusion

Although all children with TDF-associated nephrotoxicity had biochemical resolution on drug withdrawal, renal monitoring of children receiving TDF is important, especially with the co-administration of PIs. Postmarketing surveillance is essential in the paediatric setting.

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Conflict of interest

No funding has been received for the conduct of this study. YL, HL and CF declare that they have no conflicts of interest.

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Authors and Affiliations

  1. The Family Clinic, Department of Paediatrics, Imperial College Healthcare NHS Trust, London, UK

    Yinru Lim, Hermione Lyall & Caroline Foster

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  1. Yinru Lim
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  2. Hermione Lyall
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Correspondence to Yinru Lim.

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Lim, Y., Lyall, H. & Foster, C. Tenofovir-Associated Nephrotoxicity in Children with Perinatally-Acquired HIV Infection: A Single-Centre Cohort Study. Clin Drug Investig 35, 327–333 (2015). https://doi.org/10.1007/s40261-015-0287-5

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