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Tenofovir-Ritonavir Combination Therapy Linked to Nephrotoxicity in HIV Patients: Presented at CROI

By Ed Susman

LOS ANGELES, CA -- March 5, 2007 -- Treatment of patients infected with HIV with regimens that contain tenofovir and ritonavir appear to be associated with kidney damage, but regimens with tenofovir alone do hot have that effect, doctors reported here at the 14^th Conference on Retroviruses and Opportunistic Infections (CROI).

"Tenofovir disoproxil fumarate has been associated with renal toxicity in previous reports," noted Christopher Mathews, MD, director, Owen Clinic, University of California San Diego (UCSD), and professor of clinical medicine, UCSD Medical Center, San Diego, California, United States.

But after analysing records of HIV-infected patients treated at the Owen Clinic, Dr. Matthews was able to report, "In our cohort, low dose ritonavir in tenofovir containing regimens was associated with nephrotoxicity by two Modification of Diet in Renal Disease Study Group (MDRD) glomerular filtration rate metrics in patients without pre-existing renal disease, while tenofovir alone posed no additional risk."

The protease inhibitor ritonavir in low doses is frequently used in subtherapeutic doses to increase exposure of other drugs -- particularly protease inhibitors -- to circulating HIV. Why ritonavir in combination with tenofovir would cause kidney function deterioration while tenofovir by itself would not is clear, Dr. Matthews said in his poster presentation on February 28^th.

In mining the Owen Clinic database, the researchers identified 4,271 patients. They excluded 1,766 patients who were not on antiretroviral treatment and then excluded another 1,735 patients who did not have baseline creatinine measurements. Another 91 patients with low baseline creatinine clearance were also excluded from the study.

The remaining 635 patients included 380 who had no experience with the nucleotide reverse transcriptase inhibitor tenofovir -- 91 who previously were treated with tenofovir but not in regimens containing ritonavir, and 184 patients whose regimens included both tenofovir and ritonavir.

Time to decreased glomerular filtration rate was statistically increased if the patients were on the 2 drugs in both standard calculations of the filtration rate (P = .0067; P = .0053), Dr. Mathews said.

The study was supported by the UCSD Center for AIDS Research.


[Presentation title: Risk Factors for Tenofovir-associated Nephrotoxicity Identified in an HIV Clinic Cohort. Abstract 833]

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