XIX International AIDS Conference

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Complicated atazanavir-associated cholelithiasis: a report of eight documented cases among 11 cases

Y. Poinsignon1, F. Borsa-Lebas2, H. Jantzem3, S. Rakotondravelo1, E. Polard4, N. Massy5, F. Giroux6, H. Kerspern7, A. Meskar7, G. Hue8, C. Arvieux9, P. Tattevin9

1Centre Hospitalier Bretagne Atlantique, Médecine Interne, Vannes, France, 2Centre Hospitalier Universitaire Charles Nicolle, Maladies Infectieuses, Rouen, France, 3Centre Hospitalier Universitaire La Cavale Blanche, Centre Régionnal de Pharmaco-Vigilance, Brest, France, 4Centre Hospitalier Universitaire Pontchaillou, Centre Régionnal de Pharmaco-Vigilance, Rennes, France, 5Centre Hospitalier Universitaire Charles Nicolle, Centre Régionnal de Pharmaco-Vigilance, Rouen, France, 6Centre Hospitalier Bretagne Atlantique, Biochimie, Vannes, France, 7Centre Hospitalier Universitaire La Cavale Blanche, Biochimie, Brest, France, 8Centre Hospitalier Universitaire Charles Nicolle, Biochimie, Rouen, France, 9Centre Hospitalier Universitaire Pontchaillou, Maladies Infectieuses, Rennes, France

Background: Atazanavir based-antiretroviral combinations are among the most common antiretrovirals regimen, in 2012. Although hyperbilirubinemia is a characteristic adverse event, its clinical consequences are usually limited to yellow coloration of conjunctivae or skin. Drinking enough water prevent urinary stones.
Methods: Retrospective study of cases reported to the pharmacovigilance department registries of two French hospitals. Only cases where spectrophotometry analysis of biliary stones revealed significant levels of atazanavir were included.
Results: From 2008 to 2011, 11 patients have been cholecystectomised, 8 cases fulfilled inclusion criteria. All patients were male, with a mean age of 49 years (range, 36-82), and a mean body mass index of 23 kg/m2. Past medical stories were remarkable for indinavir-associtaed urinary lithiasis (n=2), and didanosine-induced acute pancreatitis (n=1). 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). At the time of cholelithiasis diagnosis, patients were treated with atazanavir for a mean duration of 50 months, their mean CD4 cell count was 683 ± 310/mm3, and all had undetectable plasma viral load. All patients were icteric and presented with abdominal pain. Final diagnosis was acute pancreatitis (n=3), acute cholecystitis (n=3), and angiocholitis (n=1). Seven patients underwent per-coelioscopic cholecystectomy, and three underwent per-endoscopic sphincterotomy (two patients had both). Atazanavir was found in 8 biliary stones analyzed, representing 10% to 100% of the total weight (mean 72%). Atazanavir was discontinued in 7 patients. All patients survived and none relapsed, with a mean follow-up of 3 years. 3 other patients do not have atazanavir in calculi but various components : bilirubinate calcium, carbapatite and cholesterol.
Conclusions: Due to its biliary elimination, and its propensity to cristallyze, as demonstrated in series of atazanavir-induced urinary lithiasis, atazanavir may be responsible of cholelithiasis, with severe complications.


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