Laird Harrison

September 24, 2012

September 24, 2012 (San Francisco, California) — Patients taking ritonavir-boosted atazanavir (ATV/r) are 10 times more likely to develop kidney stones than patients taking other protease inhibitors, according to a new study.

Because kidney stones were likely to recur if the patients continued taking ATV/r, lead author Yohei Hamada, MD, a clinical fellow at the National Center for Global Health and Medicine in Tokyo, Japan, and colleagues recommend discontinuing the drug in any patient with kidney stones.

Dr. Hamada reported the findings here at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Ritonavir-boosted atazanavir is a risk factor for kidney stones, so it should be introduced very carefully in patients with predisposing factors for kidney stones," he told Medscape Medical News.

"To be honest, I think we should avoid prescribing it to patients who have renal impairment," he added.

Protease Inhibitors

The researchers compared 465 HIV patients taking ATV/r with 773 HIV patients taking other protease inhibitors from January 1, 2004 to June 30, 2010. They followed the patients until June 30, 2011.

The other protease inhibitors patients in the study were taking were lopinavir, ritonavir-boosted lopinavir, ritonavir-boosted fosamprenavir, and ritonavir-boosted darunavir.

The researchers diagnosed new stones after the onset of acute flank pain plus new-onset hematuria confirmed by a urine dipstick test, documentation of stones (such as obstruction or dilation of the ureter by radiology), or stone passage confirmed by either the patient or attending physician

Kidney stones were diagnosed in 31 patients taking ATV/r and in 4 patients taking other protease inhibitors (6.70% vs 0.52%; P < .01).

The researchers estimated an incidence of 23.7 stones per 1000 person-years with ATV/r and 2.2 per 1000 person-years with the other protease inhibitors. The crude hazard ratio for renal stones in the ATV/r group was 10.4 (95% confidence level [CL], 3.69 to 29.6).

The researchers conducted a multivariate analysis to see if other factors could explain the increased risk for kidney stones in the ATV/r group. After adjustment for age, sex, weight, estimated glomerular filtration rate, baseline serum uric acid, and previous exposure to indinavir, the hazard ratio was 10.1 (95% CL, 3.49 to 29.1).

Median time from the commencement of ATV/r to the diagnosis of a kidney stone was 24.5 months (interquartile range, 14.7 to 34.6 months) in the 31 patients on ATV/r who developed stones.

Of the 18 patients who continued on ATV/r after developing a kidney stone, 6 (33.3%) developed another stone. The mean time to recurrence was 4.9 months (interquartile range, 1.5 to 12.2 months).

However, the patients who discontinued ATV/r after a stone was diagnosed did not have any more stones during the observation period (250.6 person-months).

Underlines Danger

This finding underlines the danger of kidney stones with this drug, Victoire de Lastours, MD, infectious disease specialist at Sorbonne University in Paris, France, told Medscape Medical News.

"Now that we know this, it's probably not very ethical to continue a patient who has a stone on this treatment," she said. "More and more of these reports are coming out. People are trying to understand why these patients are at risk."

Dr. de Lastours was not associated with this study. A separate study presented at the meeting by Dr. de Lastours showed that patients taking r/ATV and ritonavir-boosted darunavir had crystals of these drugs in their urine.

The presence of crystals increases the risk for a kidney stone. If laboratory tests show such crystals, Dr. de Lastours recommended that the patients stay hydrated.

52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract H-888. Presented September 10, 2012.