Kidney Disease Risk Higher with Longer Exposure to Antiretrovirals, Study Finds

Chronic kidney disease developed in association with exposure to antiretrovirals in people with initially normal levels of estimated glomerular filtration rate (eGFR) was not limited to increased incidence immediately after starting therapy but in fact increased over time and exposure, according to a study results reviewed at the annual Conference on Retroviruses and Opportunistic Infections in Seattle.

Presenter Amanda Mocroft of University College London, in London England, discussed the study from the D.A.D study group, Data Collection on Adverse Events of Anti-HIV Drugs. She began her talk noting that several studies have shown an association to renal impairment and the use of antiretroviral drugs that include tenofovir, ritonavir-boosted atazanavir, and lopinavir and other ritonavir-boosted protease inhibitors or abacavir.

There has been controversy over whether this risk is cumulative and increases as exposure to antiretrovirals increases over time or on the other hand is “a so called early hit,” Mocroft said. But there is limited data in persons with a normal eGFR to determine if their risk of renal impairment gets continually higher or whether it levels off with long term antiretroviral exposure of 5 or more years, she said.

This study aimed to evaluate if the reported association between chronic kidney disease and antiretrovirals is cumulative among persons with initially normal renal function. The reviewed drugs included tenofovir, ritonavir-boosted atazanavir, lopinavir and other ritonavir-boosted protease inhibitors or abacavir.

Researchers looked at data from 2004 to 2012 and followed participantsfrom baseline until the earliest of chronic kidney disease, Mocroft said.Those who developed chronic kidney disease had a higher proportion of hypertension, prior cardio vascular disease and diabetes and were considerably older than those who did not develop the disease.

The data showed that out of 23,560 people included in the study, 210 persons developed chronic kidney disease after an average of 6.3 years follow up.

In her presentation, Mocroft reviewed a slide that showed the increased risks of tenofovir, ritonavir-boosted atazanavir, and lopinavirat 1, 2 and 5 years. While there was a modest effect per year, there was a cumulative risk at 5 years, for example the 12% per year associated with tenofovir equates to a 74% increase instance after 5 years, she said.

“It’s worth also remembering that the underlying risks of chronic kidney disease varies considerably in different patient populations and the increased risk will be most significant in those at the highest risk of chronic kidney disease,” she said.

Researchers concluded from the data collected that there is a cumulative increased risk of chronic kidney disease when there is increased exposure to tenofovir, ritonavir-boosted atazanavir, and lopinavirin persons with an initially normal eGFR.

To determine if the risk for chronic kidney disease continues to increase with more than 6 years of exposure to antiretrovirals, study participants would have to be followed for a considerably longer time, Mocroft noted.