The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: The first 4 years

Mark R. Nelson, Christine Katlama, Julio S. Montaner, David A. Cooper, Brian Gazzard, Bonaventura Clotet, Adriano Lazzarin, Knud Schewe, Joep Lange, Christina Wyatt, Sue Curtis, Shan Shan Chen, Stephen Smith, Norbert Bischofberger, James F. Rooney

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Abstract

OBJECTIVE: To characterize the safety profile of tenofovir disoproxil fumarate (DF) for the treatment of HIV infection in adults over the first 4 years of use. METHODS: A tenofovir DF expanded access program (EAP) was initiated in 2001; safety data were examined from this program and from the manufacturer's database, which contained reports of all postmarketing adverse drug reactions received up to 30 April 2005. Specific analyses were performed to characterize the renal safety of tenofovir DF. RESULTS: The EAP enrolled 10 343 patients; serious adverse events (SAEs) were reported in 631 (6%). A renal SAE of any type was observed in 0.5% of patients, and graded elevations in serum creatinine occurred in 2.2% of the patients evaluated. In a multivariate analysis, baseline risk factors for the development of increased serum creatinine on-study were elevated serum creatinine, concomitant nephrotoxic medications, low body weight, advanced age, and lower CD4 cell count. For postmarketing safety data (455 392 person-years of exposure to tenofovir DF) the most commonly reported serious adverse drug reactions were renal events, with a distribution by type similar to that observed in the EAP. Bone abnormalities were infrequently reported in either the EAP or the postmarketing safety databases. No new unexpected toxicities were identified in postmarketing safety surveillance. CONCLUSIONS: The data demonstrate a favorable safety profile for tenofovir DF in the treatment of adults with HIV infection. Risk factors for development of nephrotoxicity can be identified and may be useful in managing those patients at greatest risk.

Original languageEnglish
Pages (from-to)1273-1281
Number of pages9
JournalAIDS (London, England)
Volume21
Issue number10
DOIs
Publication statusPublished - Jun 2007

Fingerprint

Tenofovir
HIV Infections
Safety
Creatinine
Drug-Related Side Effects and Adverse Reactions
Kidney
Therapeutics
Serum
Databases
CD4 Lymphocyte Count

Keywords

  • Adverse events
  • Expanded access
  • HIV
  • Nephrotoxicity
  • Postmarketing surveillance
  • Renal
  • Safety
  • Tenofovir DF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Nelson, M. R., Katlama, C., Montaner, J. S., Cooper, D. A., Gazzard, B., Clotet, B., ... Rooney, J. F. (2007). The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: The first 4 years. AIDS (London, England), 21(10), 1273-1281. https://doi.org/10.1097/QAD.0b013e3280b07b33

The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults : The first 4 years. / Nelson, Mark R.; Katlama, Christine; Montaner, Julio S.; Cooper, David A.; Gazzard, Brian; Clotet, Bonaventura; Lazzarin, Adriano; Schewe, Knud; Lange, Joep; Wyatt, Christina; Curtis, Sue; Chen, Shan Shan; Smith, Stephen; Bischofberger, Norbert; Rooney, James F.

In: AIDS (London, England), Vol. 21, No. 10, 06.2007, p. 1273-1281.

Research output: Contribution to journalArticle

Nelson, MR, Katlama, C, Montaner, JS, Cooper, DA, Gazzard, B, Clotet, B, Lazzarin, A, Schewe, K, Lange, J, Wyatt, C, Curtis, S, Chen, SS, Smith, S, Bischofberger, N & Rooney, JF 2007, 'The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: The first 4 years', AIDS (London, England), vol. 21, no. 10, pp. 1273-1281. https://doi.org/10.1097/QAD.0b013e3280b07b33
Nelson, Mark R. ; Katlama, Christine ; Montaner, Julio S. ; Cooper, David A. ; Gazzard, Brian ; Clotet, Bonaventura ; Lazzarin, Adriano ; Schewe, Knud ; Lange, Joep ; Wyatt, Christina ; Curtis, Sue ; Chen, Shan Shan ; Smith, Stephen ; Bischofberger, Norbert ; Rooney, James F. / The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults : The first 4 years. In: AIDS (London, England). 2007 ; Vol. 21, No. 10. pp. 1273-1281.
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abstract = "OBJECTIVE: To characterize the safety profile of tenofovir disoproxil fumarate (DF) for the treatment of HIV infection in adults over the first 4 years of use. METHODS: A tenofovir DF expanded access program (EAP) was initiated in 2001; safety data were examined from this program and from the manufacturer's database, which contained reports of all postmarketing adverse drug reactions received up to 30 April 2005. Specific analyses were performed to characterize the renal safety of tenofovir DF. RESULTS: The EAP enrolled 10 343 patients; serious adverse events (SAEs) were reported in 631 (6{\%}). A renal SAE of any type was observed in 0.5{\%} of patients, and graded elevations in serum creatinine occurred in 2.2{\%} of the patients evaluated. In a multivariate analysis, baseline risk factors for the development of increased serum creatinine on-study were elevated serum creatinine, concomitant nephrotoxic medications, low body weight, advanced age, and lower CD4 cell count. For postmarketing safety data (455 392 person-years of exposure to tenofovir DF) the most commonly reported serious adverse drug reactions were renal events, with a distribution by type similar to that observed in the EAP. Bone abnormalities were infrequently reported in either the EAP or the postmarketing safety databases. No new unexpected toxicities were identified in postmarketing safety surveillance. CONCLUSIONS: The data demonstrate a favorable safety profile for tenofovir DF in the treatment of adults with HIV infection. Risk factors for development of nephrotoxicity can be identified and may be useful in managing those patients at greatest risk.",
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AU - Cooper, David A.

AU - Gazzard, Brian

AU - Clotet, Bonaventura

AU - Lazzarin, Adriano

AU - Schewe, Knud

AU - Lange, Joep

AU - Wyatt, Christina

AU - Curtis, Sue

AU - Chen, Shan Shan

AU - Smith, Stephen

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AU - Rooney, James F.

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N2 - OBJECTIVE: To characterize the safety profile of tenofovir disoproxil fumarate (DF) for the treatment of HIV infection in adults over the first 4 years of use. METHODS: A tenofovir DF expanded access program (EAP) was initiated in 2001; safety data were examined from this program and from the manufacturer's database, which contained reports of all postmarketing adverse drug reactions received up to 30 April 2005. Specific analyses were performed to characterize the renal safety of tenofovir DF. RESULTS: The EAP enrolled 10 343 patients; serious adverse events (SAEs) were reported in 631 (6%). A renal SAE of any type was observed in 0.5% of patients, and graded elevations in serum creatinine occurred in 2.2% of the patients evaluated. In a multivariate analysis, baseline risk factors for the development of increased serum creatinine on-study were elevated serum creatinine, concomitant nephrotoxic medications, low body weight, advanced age, and lower CD4 cell count. For postmarketing safety data (455 392 person-years of exposure to tenofovir DF) the most commonly reported serious adverse drug reactions were renal events, with a distribution by type similar to that observed in the EAP. Bone abnormalities were infrequently reported in either the EAP or the postmarketing safety databases. No new unexpected toxicities were identified in postmarketing safety surveillance. CONCLUSIONS: The data demonstrate a favorable safety profile for tenofovir DF in the treatment of adults with HIV infection. Risk factors for development of nephrotoxicity can be identified and may be useful in managing those patients at greatest risk.

AB - OBJECTIVE: To characterize the safety profile of tenofovir disoproxil fumarate (DF) for the treatment of HIV infection in adults over the first 4 years of use. METHODS: A tenofovir DF expanded access program (EAP) was initiated in 2001; safety data were examined from this program and from the manufacturer's database, which contained reports of all postmarketing adverse drug reactions received up to 30 April 2005. Specific analyses were performed to characterize the renal safety of tenofovir DF. RESULTS: The EAP enrolled 10 343 patients; serious adverse events (SAEs) were reported in 631 (6%). A renal SAE of any type was observed in 0.5% of patients, and graded elevations in serum creatinine occurred in 2.2% of the patients evaluated. In a multivariate analysis, baseline risk factors for the development of increased serum creatinine on-study were elevated serum creatinine, concomitant nephrotoxic medications, low body weight, advanced age, and lower CD4 cell count. For postmarketing safety data (455 392 person-years of exposure to tenofovir DF) the most commonly reported serious adverse drug reactions were renal events, with a distribution by type similar to that observed in the EAP. Bone abnormalities were infrequently reported in either the EAP or the postmarketing safety databases. No new unexpected toxicities were identified in postmarketing safety surveillance. CONCLUSIONS: The data demonstrate a favorable safety profile for tenofovir DF in the treatment of adults with HIV infection. Risk factors for development of nephrotoxicity can be identified and may be useful in managing those patients at greatest risk.

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