Cumulative exposure to ritonavir-boosted atazanavir is associated with cholelithiasis in patients with HIV-1 infection

This study aimed to examine the effect of long-term treatment with ritonavir-boosted atazanavir (atazanavir/ritonavir) on cholelithiasis. A single-centre, cross-sectional study was conducted to elucidate the prevalence of cholelithiasis in patients with HIV-1 infection who underwent abdominal ultrasonography between January 2004 and March 2013. Univariate and multivariate logistic regression analyses were applied to estimate the effects of 2 years of atazanavir/ritonavir exposure on cholelithiasis as the primary exposure. Of the 890 study patients, 84 (9.4) had 2 years of atazanavir/ritonavir exposure. Cholelithiasis was twice as frequent in those treated for 2 years with atazanavir/ritonavir [15 (18) of 84 patients] compared with those treated for 2 years [72 (8.9) of 806 patients] (P0.018). Univariate analysis showed a significant association between 2 years of atazanavir/ritonavir exposure and cholelithiasis (OR2.216; 95 CI1.2064.073; P0.010) and the association almost persisted in multivariate analysis (adjusted OR1.806; 95 CI0.9223.537; P0.085). Long-term treatment (2 years) with other commonly used protease inhibitors, such as ritonavir-boosted lopinavir and ritonavir-boosted darunavir, was not associated with cholelithiasis in univariate and multivariate analysis. Additional analysis showed that 1 year of exposure to atazanavir/ritonavir was significantly associated with cholelithiasis (OR1.857; 95 CI1.0733.214; P0.027), whereas 1 year of exposure to ritonavir-boosted lopinavir and ritonavir-boosted darunavir was not. Long-term treatment of patients with HIV-1 infection for 2 years with atazanavir/ritonavir was associated with an increased risk of cholelithiasis compared with patients with shorter exposure. Long-term exposure to atazanavir/ritonavir appears to increase the risk of cholelithiasis in patients with HIV-1 infection.