Background: Tenofovir disoproxil fumarate (TDF) is neither licensed for use nor extensively studied in HIV-infected children. The only available formulation is an adult tablet, introducing the possibility of dosing errors in children. TDF interacts with other antiretrovirals and has been associated with decline in renal function and CD4 count. We describe the use of TDF in a cohort of HIV-1–infected children in the United Kingdom and Ireland.
Methods: Children ever prescribed TDF and followed in the Collaborative HIV Pediatric Study cohort since 2001 were included in analyses of dosing, adverse events, and virologic and immunologic response. Suspected adverse drug reactions to TDF reported to the Medicines and Healthcare products Regulatory Agency during the same time were also reviewed.
Results: One hundred fifty-nine of 1253 children had taken TDF. They were older and had clinically more advanced disease than the rest of the cohort. Eighteen percent received >120% and 37% received <80% of the suggested pediatric dose (8 mg/kg). Thirty-seven percent of new TDF regimens contained didanosine (ddI), though few since 2005. Twelve of 159 (7.5%) children experienced serious adverse events and stopped TDF permanently, 11 taking concurrent lopinavir-ritonavir, and 10 ddI; 5 had renal toxicity. Viral load suppressed to ≤50 copies/mL at 12 months in 38% of those starting TDF. Median increase in CD4 count at 12 months was +110 cells/mL (interquartile range, 9–270), but only 3 cells/mL in those taking concurrent ddI.
Conclusions: TDF seems to be an effective antiretroviral drug in this pediatric cohort, although considerable underdosing and overdosing occurs. A small number of children experienced serious adverse events while taking TDF; half were renal toxicity, most associated with concurrent ddI and lopinavir-ritonavir use.
From the *Royal Liverpool Children's NHS Trust, Liverpool, England; †MRC Clinical Trials Unit, London, England; ‡Imperial College NHS Trust, London, England; §Guy's and St Thomas’ NHS Foundation Trust, London, England; and ¶Our Lady's Hospital for Sick Children, Dublin, Ireland.
Accepted for publication September 3, 2008.
CHIPS is primarily funded by the Department of Health and in the past received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, and Abbott. This project was supported by a grant from Gilead Sciences, Inc.
A.R. has organized educational meetings using unrestricted grants from Gilead. No conflict for all other authors.
Address for correspondence: Andrew Riordan, MD, FRCPCH, Royal Liverpool Children's Hospital, Eaton Rd, Liverpool, L12 2AP, UK. E-mail: Andrew.email@example.com.