The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years.
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.
Nelson
Mark R
MR
Department of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London, UK. mark.nelson@chelwest.nhs.uk
Katlama
Christine
C
Montaner
Julio S
JS
Cooper
David A
DA
Gazzard
Brian
B
Clotet
Bonaventura
B
Lazzarin
Adriano
A
Schewe
Knud
K
Lange
Joep
J
Wyatt
Christina
C
Curtis
Sue
S
Chen
Shan-Shan
SS
Smith
Stephen
S
Bischofberger
Norbert
N
Rooney
James F
JF
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
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