By Liz Highleyman

Tenofovir (Viread, also in the Truvada and Atripla combination pills) is a component of one of 2 recommend nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbones, and is generally regarded as safe and effective.

Studies have produced conflicting data, however, about the association of tenofovir with kidney toxicity (nephrotoxicity). Clinical trials of tenofovir did not show a higher rate of nephrotoxicity in people taking tenofovir compared with placebo, but some subsequent studies with longer follow-up have indicated a small risk in people with pre-existing risk factors.

Kidney anatomy

To shed further light on this issue, Chelsea Castellano and colleagues analyzed the incidence of and risk factors for tenofovir-associated nephrotoxicity; she reported the group's findings at the XVII International AIDS Conference last week in Mexico City.

Out of a study cohort of 1574 HIV positive patients at the Duke University HIV Clinic in North Carolina (74% men; 55% African American; 37% white; median age about 44 years), the investigators identified 744 individuals who had used tenofovir for more than 3 months and who had baseline serum creatinine recorded during the year prior to tenofovir initiation. They also randomly selected 191 clinic patients who had been on antiretroviral therapy for at least 1 year but had not taken tenofovir.

Tenofovir-associated nephrotoxicity was defined as a decrease of 50% or more in the glomerular filtration rate (GFR) or a 25 mL/min or greater decrease in creatinine clearance.

The glomerular filtration rate (GFR) shows how efficiently your kidneys are removing wastes from your bloodstream.

Results

• 35 of 744 patients taking tenofovir developed nephrotoxicity (7.5%).

• 8 of the 191 control patients not taking tenofovir developed nephrotoxicity (4.2%).

• Kidney function improved in 16 of the 20 individuals with nephrotoxicity who discontinued tenofovir (80%).

• 10 of the 15 people with nephrotoxicity who stayed on tenofovir had persistently abnormal kidney function (67%).

• Significant independent predictors of developing nephrotoxicity included:

• History of opportunistic infections: odds ratio (OR) 2.40;

• Previous protease inhibitor (PI) use: OR 2.80;

• Concurrent PI use: OR 3.79;

• Chronic pain (a marker for potential use of non-steroidal anti-inflammatory drugs, or NSAIDS): OR 4.58;

• Hypertension: OR 4.79;

• Medical co-morbidities: OR 5.43;

• Concurrent nephrotoxic medications: OR 6.36.

• Diminished risk of nephrotoxicity was associated with:

• Use of tenofovir as used as part of an HAART initial regimen: OR 0.36;

Based on these findings, the researchers concluded that in a university-based HIV clinic, nephrotoxicity associated with antiretroviral use "tended to be more common among persons receiving tenofovir," and that "clinical risk factors for tenofovir-associated nephrotoxicity were readily identifiable."

They added that most tenofovir-associated nephrotoxicity was reversible following tenofovir discontinuation, but persistent if tenofovir was not discontinued.

"Tenofovir use should be avoided in patients with hypertension requiring other nephrotoxic drugs, especially if given with a PI," they recommended. "Use as part of initial NNRTI-based therapy is low risk for nephrotoxicity."

Duke University Medical Center, Durham, NC; Ryan White Clinic, Hickory, UK.

8/12/08

Reference
C Castellano, W Williams, TB Kepler, and others. Clinical predictors of tenofovir-associated nephrotoxicity in HIV-1-infected patients. XVII International AIDS Conference (AIDS 2008). Mexico City. August 3-8, 2008. Abstract WEAB0104. (Abstract)