First report: atazanavir-related gallstones (cholelithiasis)

Simon Collins, HIV i-Base

A poster presentation included the first report of atazanavir-related gallstones. [1]

Following two cases of gallstones in patients on atazanavir reported to the pharmacovigilence departments of two hospitals in western France, Poinsignon and colleagues performed a case review for all patients attending these clinics between 2008 and 2011. The review was limited to cases where spectrophotometry analysis of the stones showed significant levels of atazanavir.

They identified 11 patients (10 men, 1 woman) who had underdone cholecystectomy. Mean age was 49 years (range 32-82) and mean BMI of 23 kg/m2 and all were virally suppressed on atazanavir-based combinations (mean atazanavir duration of 50 months). The mean CD4 cell count was 683 (± 310) cells/mm3.

Co-morbidities included HCV-coinfection (n=6, of whom 1 had cirrhosis, 1 hepatocellular carcinoma, and 1 HBV and HDV co-infections), past intravenous drug use (n=3), haemophilia A (n=2), and chronic alcohol abuse (n=2). Final diagnoses included acute pancreatitis (n=3), acute cholecystitis (n=3), and angiocholitis (n=1). Ten patients underwent laperoscopic cholecystectomy, and one had endoscopic sphincterotomy (two patients had both).

Atazanavir was found in biliary stones from eight patients, composing 10% to 100% of the total weight (mean 72%), but included 4 patients with 100% composition. Three other patients did not contain atazanavir but included bilirubinate calcium, carbapatite and cholesterol. Atazanavir was boosted in 6/8 (using doses of 150 mg to 400 mg) and unboosted in 2/8. Atazanavir plasma levels for all patients were within the therapeutic range.

Biochemical and infrared spectrometry analysis of the stones led the researchers to determine this was related to direct atazanavir precipitation n 8/11 cases and to biliary elimination through the UGT1A1 metabolic pathway in 3/11 cases.

All patients switched atazanavir to raltegravir, an NNRTI or an alternative PI. All patients survived and none relapsed, with a mean follow-up of three years.

The authors noted that these cases were mostly in men coinfected with HCV with mean atazanavir exposure of four years and that based on these cases they estimated an incidence in their region of 2-2.5 cases per 1000 patients years (of atazanavir).

They also concluded, “atazanavir-treated patients with abdominal pain necessitate liver function and lipase tests as well as hepatobiliary ultrasound examination to evaluate medico-surgical care” and that possible calculus analysis must be undertaken and the case reported to drug safety surveillance systems.


This study has also been published online in July in Clinical Infectious Diseases [2] together with a new Japanese study of atazanavir-related kidney stones. [3]


  1. Poinsignon Y et al. Complicated atazanavir-associated cholelithiasis: a report of eight documented cases among 11 cases. 19th International AIDS Conference. 22-27 July 2012, Washington. Poster abstract MOPE099.
  2. Rakotondravelo S et al. Complicated atazanavir-associated cholelithiasis: a report of 14 cases. Clin Infect Dis. (2012) 55 (9): 1270-1272. doi: 10.1093/cid/cis620. First published online: 19 July 2012.
  3. Hamada Y et a. High incidence of renal stones among HIV-infected patients on ritonavir-boosted atazanavir than in those receiving other protease inhibitor–containing antiretroviral Therapy. Clin Infect Dis. (2012) 55 (9): 1270-1272. doi: 10.1093/cid/cis621. First published online: 19 July 2012. 

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