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.
From the aDepartment of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, London, UK
bDepartment of Infectious Diseases, Pitie-Salpetriere Hospital, Paris, France
cBritish Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, Canada
dNational Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
eHospital Universitari Germans Trias i Pujol and Institut de Recerca de la SIDA-Caixa Foundation, Badalona, Spain
fVita-Salute University, San Raffaele Scientific Institute, Milan, Italy
gIPM-Study Centre, Hamburg, Germany
hCenter for Poverty-Related Communicable Diseases, Academic Medical Center, University of Amsterdam, the Netherlands
iDivision of Nephrology, Mount Sinai Medical Center, New York, USA
jGilead Sciences, Inc., Cambridge, UK and Foster City, California, USA.
Received 23 August, 2006
Revised 20 December, 2006
Accepted 18 January, 2007
Correspondence to Dr M.R. Nelson, Chelsea and Westminster Hospital, 369 Fulham Rd, London SW10 9NH, UK. E-mail: firstname.lastname@example.org