Background and Objectives: The introduction of highly active anti-retroviral therapy has led to a significant decline in morbidity and mortality. Although several studies in adult populations have shown that tenofovir-disoproxil-fumarate (TDF) use is associated with a significant loss of renal function, there is still uncertainty on the long-term TDF safety profile in pediatric HIV populations, mostly in vertically HIV-infected patients. The aim of this study was to evaluate the long-term TDF renal safety profile, during a ten-year follow up. Methods: Twenty-six vertically HIV-infected patients were evaluated for a total of 132 months of follow up, monitoring anthropometric parameters, renal function, viral load and CD4+ count. Generalized estimating equations were used to evaluate the changes in anthropometric and laboratory variables. Multivariable fractional polynomials were used to test for the existence of non-linear relationships of outcomes with time and other continuous covariates. In all patients, weight, height and body mass index increased linearly with time. CD4+ count and glomerular filtration rate decreased linearly with time (p < 0.01). Results: No significant increase of serum creatinine was registered. An inverse linear relationship between time and plasma phosphate was found. Hypophosphatemia was detected in 17 patients, mostly mild. In 14 out of 17 we also genotyped single nucleotide polymorphisms rs717620 mapping in ABCC2, a gene encoding for a renal transporter. Conclusions: Our study demonstrates the relative safety of prolonged use of TDF in vertically HIV-infected children and young adults. The most relevant alteration that emerged was hypophosphatemia, appearing after 72 months of TDF therapy, mostly mild and without clinical significance.

Long-term renal effects of tenofovir-disoproxil-fumarate in vertically HIV-infected children, adolescents, and young adults: a 132-month follow-up study / V. Giacomet, P. Nannini, A. Vigano, P. Erba, A. Benincaso, G. Bedogni, D. Cattaneo, F.S. Falvella, G.V. Zuccotti. - In: CLINICAL DRUG INVESTIGATION. - ISSN 1173-2563. - 35:7(2015 Jul), pp. 419-426. [10.1007/s40261-015-0293-7]

Long-term renal effects of tenofovir-disoproxil-fumarate in vertically HIV-infected children, adolescents, and young adults: a 132-month follow-up study

V. Giacomet;P. Nannini;P. Erba;G. Bedogni;D. Cattaneo;G.V. Zuccotti
2015-07

Abstract

Background and Objectives: The introduction of highly active anti-retroviral therapy has led to a significant decline in morbidity and mortality. Although several studies in adult populations have shown that tenofovir-disoproxil-fumarate (TDF) use is associated with a significant loss of renal function, there is still uncertainty on the long-term TDF safety profile in pediatric HIV populations, mostly in vertically HIV-infected patients. The aim of this study was to evaluate the long-term TDF renal safety profile, during a ten-year follow up. Methods: Twenty-six vertically HIV-infected patients were evaluated for a total of 132 months of follow up, monitoring anthropometric parameters, renal function, viral load and CD4+ count. Generalized estimating equations were used to evaluate the changes in anthropometric and laboratory variables. Multivariable fractional polynomials were used to test for the existence of non-linear relationships of outcomes with time and other continuous covariates. In all patients, weight, height and body mass index increased linearly with time. CD4+ count and glomerular filtration rate decreased linearly with time (p < 0.01). Results: No significant increase of serum creatinine was registered. An inverse linear relationship between time and plasma phosphate was found. Hypophosphatemia was detected in 17 patients, mostly mild. In 14 out of 17 we also genotyped single nucleotide polymorphisms rs717620 mapping in ABCC2, a gene encoding for a renal transporter. Conclusions: Our study demonstrates the relative safety of prolonged use of TDF in vertically HIV-infected children and young adults. The most relevant alteration that emerged was hypophosphatemia, appearing after 72 months of TDF therapy, mostly mild and without clinical significance.
pharmacology (medical)
Settore MED/38 - Pediatria Generale e Specialistica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/287898
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