Due
to its potency, durability, and generally favorable safety and resistance profiles,
the nucleotide analogue tenofovir (brand
name Viread) is commonly used for the treatment of HIV-1 as a first-line antiretroviral
in combination with other anti-HIV drugs. (Tenofovir is also known as tenofovir
disoproxil fumarate, tenofovir DF, or TDF).
Another
clinical trial is studying the efficacy of tenofovir in improving HIV-related
dyslipidemia in treatment-experienced HIV-infected adults. The drug is under investigation
for the treatment of lamivudine-resistant
hepatitis B virus (HBV) infection in patients who are coinfected with HIV
and HBV. In recent studies, tenofovir has been characterized as a safer and perhaps
more effective drug than the nucleotide analog adefovir
dipivoxil (Hepsera) in the treatment of chronic hepatitis B.
Still,
some concerns remain about the long-term safety of tenofovir, in particular its
association with hepatic (liver-related), renal (kidney-related), and pancreatic
(pancreas-related) toxicities.
In
the present article, published in the Journal of Antimicrobial Chemotherapy
(published online in advance of print on June 7, 2007), researchers characterized
and evaluated the safety of tenofovir for the treatment of HIV infection in adults
over the first 4 years of its use.
Gilead
Sciences, the manufacturer of tenofovir, initiated a tenofovir expanded access
program (EAP) in 2001. For the current study, safety data were examined from the
EAP and from Gilead's database, which contains reports of all post-marketing adverse
drug reactions received up to April 30, 2005.
Specific
analyses were performed to characterize the renal safety of tenofovir.
Results
• The EAP enrolled 10,343
patients.
• Serious
adverse events (SAEs) were reported in 631 individuals (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 post-marketing safety data (455,392 person-years of exposure to
tenofovir), 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 post-marketing safety databases.
•
No new unexpected toxicities were identified in post-marketing safety
surveillance.
Conclusion
In
conclusion, the study authors write, "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."
Department
of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, London, UK;
Department of Infectious Diseases, Pitie-Salpetriere Hospital, Paris, France;
British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia,
Vancouver, Canada; National Centre in HIV Epidemiology and Clinical Research,
University of New South Wales, Sydney, Australia; Hospital Universitari Germans
Trias i Pujol and Institut de Recerca de la SIDA-Caixa Foundation, Badalona, Spain;
Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy; IPM-Study
Centre, Hamburg, Germany; Center for Poverty-Related Communicable Diseases, Academic
Medical Center, University of Amsterdam, the Netherlands; Division of Nephrology,
Mount Sinai Medical Center, New York, NY; Gilead Sciences, Inc., Cambridge, UK
and Foster City, CA.
Reference M
R Nelson, C Katlama, J S Montaner, D A Cooper, and others. The safety of tenofovir
disoproxil fumarate for the treatment of HIV infection in adults: the first 4
years. AIDS 21(10): 1273-1281
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The
US Food and Drug Administration (FDA) licensed tenofovir for the treatment of
chronic HIV-1 infection in adults and adolescents in October 2001. The FDA also
has approved
