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.
Judd
Ali
A
MRC Clinical Trials Unit, 222 Euston Road, London, UK. a.judd@ctu.mrc.ac.uk
Boyd
Katherine L
KL
Stöhr
Wolfgang
W
Dunn
David
D
Butler
Karina
K
Lyall
Hermione
H
Sharland
Mike
M
Shingadia
Delane
D
Riordan
Andrew
A
Gibb
Di M
DM
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