Effect of tenofovir disoproxil fumarate on risk of renal abnormality in HIV-1-infected children on antiretroviral therapy: a nested case–control study
2010; Lippincott Williams & Wilkins; Volume: 24; Issue: 4 Linguagem: Inglês
10.1097/qad.0b013e3283333680
ISSN1473-5571
AutoresAli Judd, Katherine L Boyd, Wolfgang Stöhr, David Dunn, Karina Butler, Hermione Lyall, Mike Sharland, Delane Shingadia, Andrew Riordan, Diana M. Gibb,
Tópico(s)HIV/AIDS Research and Interventions
ResumoObjective: 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). Design: 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 m2; 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 m2. 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.
Referência(s)