Effect of tenofovir disoproxil fumarate on risk of renal abnormality in HIV-1-infected children on antiretroviral therapy: a nested case-control study.
OBJECTIVE
To investigate the association between tenofovir disoproxil fumarate (TDF) use and renal abnormality in a large cohort of HIV-1-infected children on antiretroviral therapy (ART).


METHODS
Nested case-control study.


METHODS
Patients were from the Collaborative HIV Paediatric Study, a cohort of approximately 95% of HIV-1-infected children in the UK/Ireland. Serum (but not urine) biochemistry results for 2002-2008 were obtained for 456 ART-exposed children (2-18 years) seen at seven hospitals. Cases had either confirmed hypophosphataemia DAIDS grade at least 2 or estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m; three controls per case were matched by hospital. Conditional logistic regression identified risk factors for renal abnormality.


RESULTS
Twenty of 456 (4.4%) had hypophosphataemia, and one had eGFR less than 60 ml/min per 1.73 m. Ten of 20 (50%) cases versus 11 of 60 (18%) controls had taken TDF-containing ART for a median [interquartile range (IQR)] of 18 [17-20] months, as part of second-line or salvage therapy. The hypophosphataemia incidence rate was 4.3/100 person-years in the TDF group versus 0.9/100 person-years in those not exposed to TDF. In multivariable analysis, only TDF exposure in the previous 6 months was associated with hypophosphataemia [odds ratio (OR) = 4.81, 95% confidence interval (CI) 1.45-16.0, P = 0.01]. In six of 10 children with hypophosphataemia and at least four subsequent phosphate measurements, phosphate values returned to normal when TDF was stopped; in four with three measures or less, values rose but remained subnormal.


CONCLUSIONS
Hypophosphataemia was uncommon (4%), but was associated with prolonged TDF use, and was generally reversible following TDF withdrawal. Findings highlight the importance of continuing to monitor longer-term renal function, in particular tubular function, especially in those taking TDF. Further studies assessing urine biochemistry measures which more accurately indicate renal tubular damage are required.
MRC Clinical Trials Unit, 222 Euston Road, London, UK. a.judd@ctu.mrc.ac.uk
Ali
A
Judd
Katherine L
KL
Boyd
Wolfgang
W
Stöhr
David
D
Dunn
Karina
K
Butler
Hermione
H
Lyall
Mike
M
Sharland
Delane
D
Shingadia
Andrew
A
Riordan
Di M
DM
Gibb
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D019380:Anti-HIV Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004739:England / Q000453:epidemiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D017674:Hypophosphatemia / Q000139:chemically induced* / Q000453:epidemiology; D007494:Ireland / Q000453:epidemiology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects*; D016879:Salvage Therapy; D000068698:Tenofovir; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine