title: The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years.
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.
authors.affiliation: Department of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London, UK. mark.nelson@chelwest.nhs.uk
authors.forename: Mark R
authors.initials: MR
authors.lastname: Nelson
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Julio S
authors.initials: JS
authors.lastname: Montaner
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Knud
authors.initials: K
authors.lastname: Schewe
authors.forename: Joep
authors.initials: J
authors.lastname: Lange
authors.forename: Christina
authors.initials: C
authors.lastname: Wyatt
authors.forename: Sue
authors.initials: S
authors.lastname: Curtis
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Chen
authors.forename: Stephen
authors.initials: S
authors.lastname: Smith
authors.forename: Norbert
authors.initials: N
authors.lastname: Bischofberger
authors.forename: James F
authors.initials: JF
authors.lastname: Rooney
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000367:Age Factors; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D000998:Antiviral Agents / Q000627:therapeutic use; D001835:Body Weight; D018791:CD4 Lymphocyte Count; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects*; D011358:Product Surveillance, Postmarketing / Q000379:methods; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D012307:Risk Factors; D000068698:Tenofovir
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine