Clinical Features and Risk Factors for Atazanavir (ATV)-Associated Urolithiasis: A Case-Control Study

OBJECTIVES Clinical features and risk factors for atazanavir (ATV)-associated urolithiasis have not been fully investigated. METHODS We reviewed all cases of ATV-containing urolithiasis identified by infrared spectrophotometry among HIV-infected patients over a 5-year period to describe their clinical features and outcome. A case-control study was performed to identify risk factors associated with ATV-associated urolithiasis using univariate and multivariate logistic regression analyses. RESULTS 30 cases of ATV-associated urolithiasis were analyzed. Patients were mostly men (87%), median age: 45.5 years, median CD4 cell count: 443 cells/µL and 97% had plasma HIV RNA level <50 cp/mL. Median time between the initiation of ATV-containing regimen and the diagnosis of urolithiasis was 3.1 years. Patients presented with flank pain in 90% and macroscopic hematuria in 82.6%, 34% had renal dysfunction and 44.8% needed ureteroscopic treatment. In univariate analysis, chronic hepatitis C, a history of urolithiasis, prior use of indinavir, ATV duration, undetectable plasma HIV RNA, use of ritonavir as a booster and serum free bilirubin level were associated with ATV-urolithiasis. Multivariate models retained serum free bilirubin level (OR: 2.31, p<0.02) and either ATV duration (OR:  = 1.42, p = <0.03) or a history of urolithiasis (OR = 4.79, p<0.02) when adjusting on serum free bilirubin level as risk factors associated with urolithiasis. CONCLUSIONS ATV-containing urolithiasis are associated with frank clinical symptoms and may require surgical intervention. A high serum bilirubin level, a long exposure to ATV and a history of urolithiasis are risk factors for this rare adverse event.