August 7, 2008 (Mexico City) — Nephrotoxicity associated with the use of tenofovir (TDF) is a common but significant adverse event that can be better predicted and managed, according to a study presented here at the XVII International AIDS Conference.
Chelsea Castellano, MD, an investigator at the Duke University Medical Center, Durham, North Carolina, and colleagues set out to estimate the frequency of renal toxicity and to "characterize the clinical predictors of [TDF]-associated nephrotoxicity in order to assist clinicians in making treatment decisions."
The observational case-control study mined the records of patients seen at the Duke HIV Clinic from October 2001, when the US Food and Drug Administration approved TDF, to August 2007.
Of 1574 participants, the study identified 744 patients (47%) who had received TDF for at least 3 months during that period and who had a baseline creatinine measure within 1 year of initiating TDF. A randomly selected group of 191 patients who had been receiving HAART for more than 1 year but whose regimens did not contain TDF served as the control group; the 2 groups matched well in all patient characteristics.
Nephrotoxicity was defined using international consensus standards of a doubling of serum creatinine levels and/or a creatinine level higher than 1.4 mg/dL for men or higher than 1.2 mg/dL for women. A glomerular filtration rate higher than 50% was taken as a sign of renal damage.
"Persons treated with TDF had almost twice the rate of nephrotoxicity as did those who were not exposed to TDF," said Dr. Castellano. The rates were 7.5% (35 of 744 patients) in the TDF group compared with 4.2% (8 of 191 patients) in the control group, with a P value approaching statistical significance (P = .052).
Of the 35 patients in the TDF group who developed nephrotoxicity, 20 discontinued the drug and 16 had significant improvement in renal function following discontinuation. Principally because of limited treatment options, 15 patients continued to receive TDF; 10 of these continued to have persistently abnormal renal function, but the condition did not seem to worsen with time.
Dr. Castellano said that factors associated with nephrotoxicity included concurrent use of other nephrotoxic medications; comorbidities associated with nephrotoxicity, such as hypertension and diabetes; chronic pain and the presumed use of nonsteroidal anti-inflammatory drugs; current and even previous use of a protease inhibitor; and a history of opportunistic infections.
Concurrent use of a nonnucleoside reverse transcriptase inhibitor appeared to have a somewhat protective effect; "they were rarely associated with renal toxicity."
During the discussion period, a member of the audience suggested that by using the criteria of at least 3 months of TDF therapy, the study might have missed patients who discontinued the drug earlier. It thus might have underestimated the extent of nephrotoxicity. Dr. Castellano acknowledged that possibility.
"The study identified some important risk factors that we have known about," Judith Currier, MD, the chair of the session and a researcher at the University of California, San Francisco, later told Medscape HIV/AIDS. "Clinicians just need to be aware of those things. You can reduce the risk by being aware of concurrent nephrotoxic medications the patient might be on. That's in the package insert."
Kenneth Mayer, MD, a researcher at Brown University in Providence, Rhode Island, and Fenway Community Health in Boston, Massachusetts, said it is important to screen patients for comorbidities that may impair renal function. He called TDF an important and useful drug but said it has to be used appropriately.
The study did not receive any commercial support. The study was conducted using operational funds from the Duke University Medical Center and support from the National Institutes of Health. Dr. Castellano, Dr. Currier, and Dr. Mayer have disclosed no relevant financial relationships.
XVII International AIDS Conference: Abstract WEAB0104. Presented August 6, 2008.
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Cite this: Bob Roehr. Clinical Factors Predict Tenofovir Nephrotoxicity in HIV-Infected Patients - Medscape - Aug 08, 2008.