Background:  Tenofovir (TDF) is prescribed off-license for children using the adult tablet formulation. It has been associated with impaired renal function but there are few data in children. We describe renal function and phosphate levels in children in the United Kingdom and Ireland on TDF and other ART.

Methods:  Descriptive data were from the Collaborative HIV Paediatric Study, a cohort of ~95% of HIV-1-infected children treated in the United Kingdom and Ireland. Suspected adverse drug reactions were identified from reports to CHIPS and from voluntary, UK-wide, “Yellow Card” adverse drug reaction reporting. Biochemistry results from 2002 onwards were obtained for 456 ART-exposed children (2 to 18 years) seen at 7 hospitals. For the case control analysis, cases had confirmed hypophosphatemia DAIDS grade ≥2; 3 controls per case were matched by hospital of attendance and censored at the time of the case’s event.

Results:  Of 1252 children in CHIPS, 159 had ever taken TDF. They were older at last follow-up (median 14.5 vs 10.6 years, p <0.001) and more had AIDS when starting ART (35 vs 23%, p <0.001) than the rest of the cohort; 18% had >120% and 37% <80% of the recommended pediatric TDF dose (8 mg/kg); 6 had a suspected renal adverse drug reaction (PRTD/renal toxicity [5], renal failure [1]); of whom 5 took concurrent didanosine (ddI) + lopinavir/ritonavir (LPV/r) and subsequently stopped TDF. Biochemistry data indicated that 20 children had hypophosphatemia (including 4 of 6 with suspected TDF adverse drug reactions) of whom results for 8 fell within the hospital normal range, and 1 had an estimated glomerular filtration rate ≤60 mL/min/1.73 m² (Schwartz formula). Of these cases, 50% (10 of 20) vs 18% (11 of 60) of the controls had prior TDF exposure (p = 0.005); hypophosphatemia in the 10 cases on TDF occurred at median 18 months (IQR 17 to 20) post-TDF start. TDF exposure in the previous 6 months was associated with hypophosphatemia (OR 4.8, 95%CI 1.4 to 16.0), but recent use of other ART, baseline CD4/HIV-1 RNA, CDC stage, and sociodemographics were not.

Conclusions:  Although unlicensed in children, TDF is prescribed in this cohort, although considerable under/overdosing occurs. Among these children, 6 had suspected renal adverse drug reactions while on TDF, most while also taking ddI+LPV/r. Overall, serum phosphate and estimated glomerular filtration rate levels were stable 12 months after starting TDF but renal events happened later. Recent TDF exposure was associated with higher odds of hypophosphatemia, suggestive of tubular leak, however numbers were small, and 40% values were within the hospital normal range. Longer term renal outcome data are needed, as well as data on bone mineral density.