Jim Kling

February 27, 2015

SEATTLE — In patients with HIV who are taking tenofovir, ritonavir-boosted atazanavir, or ritonavir-enhanced lopinavir, the risk for chronic kidney disease increases over time, new research shows.

Previous studies have suggested that antiretroviral drugs can cause chronic kidney disease. "We wanted to look at that association more thoroughly," said study investigator Lene Ryom, MD, from the University Hospital of Copenhagen, Denmark.

"We wanted to see if we could determine whether the nature of the association is an ongoing effect or an on–off effect," she told Medscape Medical News.

Dr Ryom presented the results here at the Conference on Retroviruses and Opportunistic Infections 2015.

The researchers followed 23,560 participants in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Anyone with a baseline estimated glomerular filtration rate (eGFR) below 90 mL/min per 1.73 m² was excluded from the study.

In the study cohort, median baseline eGFR was 110 mL/min per 1.73 m², median age was 39 years, and median CD4 count was 440 cells/mm³.

Chronic kidney disease was defined as an eGFR below 60 mL/min per 1.73 m² on two occasions at least 3 months apart.

Over a mean follow-up of 6.3 years, there were 210 cases of chronic kidney disease (0.9%; incidence, 1.48 per 1000 person-years of follow-up; 95% confidence interval [CI], 1.28 - 1.68).

The incidence of chronic kidney disease increased with more exposure to tenofovir, ritonavir-boosted atazanavir, ritonavir-enhanced lopinavir, ritonavir-added protease inhibitors, and abacavir.

Trends were significant for tenofovir, ritonavir-boosted atazanavir, and ritonavir-enhanced lopinavir after adjustment for other factors that can affect the odds of developing chronic kidney disease, but not for ritonavir-added protease inhibitors or abacavir.

Table. Incidence Rate Ratios for Chronic Kidney Disease

Therapy 1 Year 2 Years 5 Years
Tenofovir 1.12 1.25 1.74
Ritonavir-boosted atazanavir 1.27 1.61 3.27
Ritonavir-enhanced lopinavir 1.16 1.35 2.11


After patients being treated with tenofovir went off the drug, the incidence rate ratio declined over time. However, 2 years after discontinuation, the rate was still higher in these patients than in those never exposed to tenofovir (adjusted incidence rate ratio, 2.47; 95% CI, 1.36 - 4.48).

"I think the data show quite thoroughly that for tenofovir, ritonavir-boosted atazanavir, and ritonavir-enhanced lopinavir, there's a very linear association, meaning that the longer you're on these drugs, the higher your risk of developing chronic kidney disease," said Dr Ryom.

This is "a confirmation of what we've seen in other studies, that there's an association between chronic kidney disease and different antiretrovirals," David Hardy, MD, from the University of California at Los Angeles, who attended the presentation, told Medscape Medical News.

There is a linear risk, said Paul Sax, MD, from Brigham and Women's Hospital in Boston, who presented results on the improved renal safety profile of a second-generation tenofovir drug during the session.

"Clinicians have long been aware that cumulative exposure to tenofovir likely increases the risk of nephrotoxicity. What perhaps is less well known is that the effect of atazanavir on reducing renal function is just as strong, if not stronger," Dr Sax told Medscape Medical News.

"We should be particularly vigilant about monitoring renal function regularly in our HIV patients on these antiretrovirals, especially those who have other risk factors for renal disease," he added.

Dr Ryom has disclosed no relevant financial relationships. Dr Hardy reports being a consultant for, serving on advisory boards for, and receiving research grants from Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, GlaxoSmithKline, Pharmaceuticals, and ViiV. Dr Sax reports being a consultant for Gilead and being an advisor for most of the companies in the HIV field.

Conference on Retroviruses and Opportunistic Infections (CROI) 2015: Abstract 142. Presented February 26, 2015.


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