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Published in: BMC Infectious Diseases 1/2012

Open Access 01-12-2012 | Research article

Renal function in HIV-infected children and adolescents treated with tenofovir disoproxil fumarate and protease inhibitors

Authors: Giuseppe Pontrelli, Nicola Cotugno, Donato Amodio, Paola Zangari, Hyppolite K Tchidjou, Stefania Baldassari, Paolo Palma, Stefania Bernardi

Published in: BMC Infectious Diseases | Issue 1/2012

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Abstract

Background

Kidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART). Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF) alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI).

Methods

Serum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR), had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18) on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI.

Results

Forty-nine patients were studied (57% female, mean age 14). Sixty-three percent were treated with ART containing TDF (Group A), and 37% without TDF (Group B); 47% with concomitant use of TDF and PI (Group C) and 53% without this combination (Group D). The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m2 at baseline to 128.9 after 2 years (p = 0.006) in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (p = 0.0003) and in TDF+PI group (p = 0.0128) after 2 years. Five patients (10%) developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2), and four of them were on TDF+PI.

Conclusions

Renal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.
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Literature
1.
go back to reference D'Arminio Monforte A, Sabin CA, Phillips A, et al: The changing incidence of AIDS events in patients receiving highly active antiretroviral therapy. Arc Intern Med. 2005, 165: 416-423.CrossRef D'Arminio Monforte A, Sabin CA, Phillips A, et al: The changing incidence of AIDS events in patients receiving highly active antiretroviral therapy. Arc Intern Med. 2005, 165: 416-423.CrossRef
2.
go back to reference Chiappini E, Galli L, Tovo PA, et al: Changing patterns of clinical events in perinatally HIV-1-infected children during the era of HAART. AIDS. 2007, 21: 1607-1615. 10.1097/QAD.0b013e32823ecf5b.CrossRefPubMed Chiappini E, Galli L, Tovo PA, et al: Changing patterns of clinical events in perinatally HIV-1-infected children during the era of HAART. AIDS. 2007, 21: 1607-1615. 10.1097/QAD.0b013e32823ecf5b.CrossRefPubMed
4.
go back to reference Roling J, Schmid H, Fischereder M, et al: HIV-Associated Renal Diseases and Highly Active Antiretroviral Therapy-Induced Nephropathy. Clin Infect Dis. 2006, 42: 1488-1495. 10.1086/503566.CrossRefPubMed Roling J, Schmid H, Fischereder M, et al: HIV-Associated Renal Diseases and Highly Active Antiretroviral Therapy-Induced Nephropathy. Clin Infect Dis. 2006, 42: 1488-1495. 10.1086/503566.CrossRefPubMed
6.
go back to reference Lee JC, Marosok RD: Acute tubular necrosis in a patient receiving tenofovir. AIDS. 2003, 17: 2543-2544. 10.1097/00002030-200311210-00021.CrossRefPubMed Lee JC, Marosok RD: Acute tubular necrosis in a patient receiving tenofovir. AIDS. 2003, 17: 2543-2544. 10.1097/00002030-200311210-00021.CrossRefPubMed
7.
go back to reference Creput C, Gonzalez-Canali G, Hill G, et al: Renal lesions in HIV-1-positive patient treated with tenofovir. AIDS. 2003, 17: 935-937. 10.1097/00002030-200304110-00026.CrossRefPubMed Creput C, Gonzalez-Canali G, Hill G, et al: Renal lesions in HIV-1-positive patient treated with tenofovir. AIDS. 2003, 17: 935-937. 10.1097/00002030-200304110-00026.CrossRefPubMed
8.
go back to reference Barrios A, Garcia-Benayas T, Gonzalez-Lahoz J, et al: Tenofovir related nephrotoxicity in HIV-infected patients. AIDS. 2004, 18: 960-963. 10.1097/00002030-200404090-00019.CrossRefPubMed Barrios A, Garcia-Benayas T, Gonzalez-Lahoz J, et al: Tenofovir related nephrotoxicity in HIV-infected patients. AIDS. 2004, 18: 960-963. 10.1097/00002030-200404090-00019.CrossRefPubMed
9.
go back to reference Zimmermann AE, Pizzoferrato T, Bedford J, et al: Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions. Clin Infect Dis. 2006, 42: 283-290. 10.1086/499048.CrossRefPubMed Zimmermann AE, Pizzoferrato T, Bedford J, et al: Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions. Clin Infect Dis. 2006, 42: 283-290. 10.1086/499048.CrossRefPubMed
10.
go back to reference Izzedine H, Launay-Vacher V, Isnard-Bagnis C, et al: Drug induced Fanconi's syndrome. Am J Kidney Dis. 2003, 41: 292-309. 10.1053/ajkd.2003.50037.CrossRefPubMed Izzedine H, Launay-Vacher V, Isnard-Bagnis C, et al: Drug induced Fanconi's syndrome. Am J Kidney Dis. 2003, 41: 292-309. 10.1053/ajkd.2003.50037.CrossRefPubMed
11.
go back to reference Gupta SK: Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. AIDS Patient Care STDS. 2008, 22: 99-103. 10.1089/apc.2007.0052.CrossRefPubMed Gupta SK: Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. AIDS Patient Care STDS. 2008, 22: 99-103. 10.1089/apc.2007.0052.CrossRefPubMed
12.
go back to reference Cirino CM, Kan VL: Hypokalemia in HIV patients on tenofovir. AIDS. 2006, 20 (12): 1671-1673. 10.1097/01.aids.0000238416.05819.09.CrossRefPubMed Cirino CM, Kan VL: Hypokalemia in HIV patients on tenofovir. AIDS. 2006, 20 (12): 1671-1673. 10.1097/01.aids.0000238416.05819.09.CrossRefPubMed
13.
go back to reference Hazra R, Gafni RI, Maldarelli F, et al: Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics. 2005, 116 (6): 846-854. 10.1542/peds.2005-0975.CrossRef Hazra R, Gafni RI, Maldarelli F, et al: Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics. 2005, 116 (6): 846-854. 10.1542/peds.2005-0975.CrossRef
14.
go back to reference Viganò A, Bedogni G, Manfredini V, et al: Long-term renal safety of tenofovir disoproxil fumarate in vertically HIV-infected children, adolescents and young adults: a 60-month follow-up study. Clin Drug Investig. 2011, 31 (6): 407-415. 10.2165/11590400-000000000-00000.CrossRefPubMed Viganò A, Bedogni G, Manfredini V, et al: Long-term renal safety of tenofovir disoproxil fumarate in vertically HIV-infected children, adolescents and young adults: a 60-month follow-up study. Clin Drug Investig. 2011, 31 (6): 407-415. 10.2165/11590400-000000000-00000.CrossRefPubMed
15.
go back to reference Hussain S, Khayat A, Tolaymat A: Nephrotoxicity in a child with perinatal HIV on tenofovir, didanosine and lopinavir/ritonavir. Pediatr Nephrol. 2006, 21: 1034-1036. 10.1007/s00467-006-0109-3.CrossRefPubMed Hussain S, Khayat A, Tolaymat A: Nephrotoxicity in a child with perinatal HIV on tenofovir, didanosine and lopinavir/ritonavir. Pediatr Nephrol. 2006, 21: 1034-1036. 10.1007/s00467-006-0109-3.CrossRefPubMed
16.
go back to reference Rollot F, Nazal E, Chauvelot-Moachon L, et al: Tenofovir-related Fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome: the role of lopinavir-ritonavirdidanosine. Clin Infect Dis. 2003, 37: 174-176. 10.1086/379829.CrossRef Rollot F, Nazal E, Chauvelot-Moachon L, et al: Tenofovir-related Fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome: the role of lopinavir-ritonavirdidanosine. Clin Infect Dis. 2003, 37: 174-176. 10.1086/379829.CrossRef
17.
go back to reference Judd A, Boyd KL, Stöhr W, et al: Effect of tenofovir disoproxil fumarate on risk of renal abnormality in HIV-1-infected children on antiretroviral therapy: a nested case-control study. AIDS. 2010, 24 (4): 525-534. 10.1097/QAD.0b013e3283333680.CrossRefPubMed Judd A, Boyd KL, Stöhr W, et al: Effect of tenofovir disoproxil fumarate on risk of renal abnormality in HIV-1-infected children on antiretroviral therapy: a nested case-control study. AIDS. 2010, 24 (4): 525-534. 10.1097/QAD.0b013e3283333680.CrossRefPubMed
18.
go back to reference Purdy JB, Gafni RI, Reynolds JC, et al: Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus. J Pediatr. 2008, 152: 582-584. 10.1016/j.jpeds.2007.12.020.CrossRefPubMedPubMedCentral Purdy JB, Gafni RI, Reynolds JC, et al: Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus. J Pediatr. 2008, 152: 582-584. 10.1016/j.jpeds.2007.12.020.CrossRefPubMedPubMedCentral
19.
go back to reference Rodriguez-Novoa S, Labarga P, Soriano V: Pharmacogenetics of tenofovir treatment. Pharmacogenomics. 2009, 10 (10): 1675-1685. 10.2217/pgs.09.115.CrossRefPubMed Rodriguez-Novoa S, Labarga P, Soriano V: Pharmacogenetics of tenofovir treatment. Pharmacogenomics. 2009, 10 (10): 1675-1685. 10.2217/pgs.09.115.CrossRefPubMed
20.
go back to reference Kiser JJ, Carten ML, Aquilante CL, et al: The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients. Clin Pharmacol Ther. 2008, 83 (2): 265-272. 10.1038/sj.clpt.6100269.CrossRefPubMed Kiser JJ, Carten ML, Aquilante CL, et al: The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients. Clin Pharmacol Ther. 2008, 83 (2): 265-272. 10.1038/sj.clpt.6100269.CrossRefPubMed
22.
go back to reference Kiser JJ, Fletcher CV, Flynn PM, et al: Pharmacokinetics of antiretroviral regimens containing tenofovir disoproxil fumarate and atazanavir-ritonavir in adolescents and young adults with human immunodeficiency virus infection. Adolescent Trials Network for HIV/AIDS Interventions. Antimicrob Agents Chemother. 2008, 52 (2): 631-637. 10.1128/AAC.00761-07.CrossRefPubMed Kiser JJ, Fletcher CV, Flynn PM, et al: Pharmacokinetics of antiretroviral regimens containing tenofovir disoproxil fumarate and atazanavir-ritonavir in adolescents and young adults with human immunodeficiency virus infection. Adolescent Trials Network for HIV/AIDS Interventions. Antimicrob Agents Chemother. 2008, 52 (2): 631-637. 10.1128/AAC.00761-07.CrossRefPubMed
23.
go back to reference Robertson EE, Ranking GO: Human renal organic anion transporters: characteristics and contributors to drug and drug metabolite excretion. Pharmacol Ther. 2006, 109: 383-389.CrossRef Robertson EE, Ranking GO: Human renal organic anion transporters: characteristics and contributors to drug and drug metabolite excretion. Pharmacol Ther. 2006, 109: 383-389.CrossRef
24.
go back to reference Gallant JE, Moore RD: Renal function with use of a tenofovir-containing initial antiretroviral regimen. AIDS. 2009, 23: 197-1975.CrossRef Gallant JE, Moore RD: Renal function with use of a tenofovir-containing initial antiretroviral regimen. AIDS. 2009, 23: 197-1975.CrossRef
25.
go back to reference Campbell LJ, Ibrahim F, Fisher M, et al: Spectrum of chronic kidney disease in HIV-infected patients. HIV Med. 2009, 10 (6): 329-336. 10.1111/j.1468-1293.2008.00691.x.CrossRefPubMed Campbell LJ, Ibrahim F, Fisher M, et al: Spectrum of chronic kidney disease in HIV-infected patients. HIV Med. 2009, 10 (6): 329-336. 10.1111/j.1468-1293.2008.00691.x.CrossRefPubMed
26.
go back to reference Riordan A, Judd A, Boyd K, et al: Tenofovir use in Human immunodeficiency virus-1-infected children in the United Kingdom and Ireland. Pediatr Infect Dis J. 2009, 28: 204-209. 10.1097/INF.0b013e31818c8d2c.CrossRefPubMed Riordan A, Judd A, Boyd K, et al: Tenofovir use in Human immunodeficiency virus-1-infected children in the United Kingdom and Ireland. Pediatr Infect Dis J. 2009, 28: 204-209. 10.1097/INF.0b013e31818c8d2c.CrossRefPubMed
27.
go back to reference Hussain S, Khayat A, Tolaymat A, et al: Nephrotoxicity in a child with perinatal HIV on tenofovir, didanosine and lopinavir/ritonavir. Pediatr Nephrol. 2006, 21 (7): 1034-1036. 10.1007/s00467-006-0109-3.CrossRefPubMed Hussain S, Khayat A, Tolaymat A, et al: Nephrotoxicity in a child with perinatal HIV on tenofovir, didanosine and lopinavir/ritonavir. Pediatr Nephrol. 2006, 21 (7): 1034-1036. 10.1007/s00467-006-0109-3.CrossRefPubMed
28.
go back to reference Soler-Palacín P, Melendo S, Noguera-Julian A, et al: Prospective study of renal function in HIV-infected pediatric patients receiving tenofovir-containing HAART regimens. AIDS. 2011, 25 (2): 171-176. 10.1097/QAD.0b013e328340fdca.CrossRefPubMed Soler-Palacín P, Melendo S, Noguera-Julian A, et al: Prospective study of renal function in HIV-infected pediatric patients receiving tenofovir-containing HAART regimens. AIDS. 2011, 25 (2): 171-176. 10.1097/QAD.0b013e328340fdca.CrossRefPubMed
29.
go back to reference Labarga P, Barreiro P, Martin-Carbonero L, et al: Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir. AIDS. 2009, 23 (6): 689-696. 10.1097/QAD.0b013e3283262a64.CrossRefPubMed Labarga P, Barreiro P, Martin-Carbonero L, et al: Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir. AIDS. 2009, 23 (6): 689-696. 10.1097/QAD.0b013e3283262a64.CrossRefPubMed
30.
go back to reference Goicoechea M, Liu S, Best B, et al: Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. J Infect Dis. 2008, 197: 102-108. 10.1086/524061.CrossRefPubMed Goicoechea M, Liu S, Best B, et al: Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. J Infect Dis. 2008, 197: 102-108. 10.1086/524061.CrossRefPubMed
31.
go back to reference Daar E, Tierney C, Fischl M, et al: ACTG 5202: final results of ABC/3TC or TDF/FTC with either EFV or ATV/r in treatment-naive HIVinfected patients. [Abstract 59LB.]. 17th Conference on Retroviruses and Opportunistic Infections. 2010, San Francisco, CA Daar E, Tierney C, Fischl M, et al: ACTG 5202: final results of ABC/3TC or TDF/FTC with either EFV or ATV/r in treatment-naive HIVinfected patients. [Abstract 59LB.]. 17th Conference on Retroviruses and Opportunistic Infections. 2010, San Francisco, CA
32.
go back to reference Kiser JJ, Aquilante CL, Anderson PL, et al: Effect of Multidrug resistance proteins 2 and 4 polymorphisms on tenofovir pharmacokinetics in HIV-infected patients. 7th International Workshop on Clinical Pharmacology of HIV Therapy. 2006, Lisbon, Portugal Kiser JJ, Aquilante CL, Anderson PL, et al: Effect of Multidrug resistance proteins 2 and 4 polymorphisms on tenofovir pharmacokinetics in HIV-infected patients. 7th International Workshop on Clinical Pharmacology of HIV Therapy. 2006, Lisbon, Portugal
33.
go back to reference Giacomet V, Mora S, Martelli L, et al: A 12-month treatment with tenofovir does not impair bone mineral accrual in HIV-infected children. J Acquir Immune Defic Syndr. 2005, 40: 448-450. 10.1097/01.qai.0000184860.62189.c8.CrossRefPubMed Giacomet V, Mora S, Martelli L, et al: A 12-month treatment with tenofovir does not impair bone mineral accrual in HIV-infected children. J Acquir Immune Defic Syndr. 2005, 40: 448-450. 10.1097/01.qai.0000184860.62189.c8.CrossRefPubMed
Metadata
Title
Renal function in HIV-infected children and adolescents treated with tenofovir disoproxil fumarate and protease inhibitors
Authors
Giuseppe Pontrelli
Nicola Cotugno
Donato Amodio
Paola Zangari
Hyppolite K Tchidjou
Stefania Baldassari
Paolo Palma
Stefania Bernardi
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2012
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-12-18

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