title: Cumulative exposure to ritonavir-boosted atazanavir is associated with cholelithiasis in patients with HIV-1 infection.
abstract: OBJECTIVE
  This study aimed to examine the effect of long-term treatment with ritonavir-boosted atazanavir (atazanavir/ritonavir) on cholelithiasis.
  
  
  METHODS
  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.
  
  
  RESULTS
  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] (P = 0.018). Univariate analysis showed a significant association between >2 years of atazanavir/ritonavir exposure and cholelithiasis (OR = 2.216; 95% CI = 1.206-4.073; P = 0.010) and the association almost persisted in multivariate analysis (adjusted OR = 1.806; 95% CI = 0.922-3.537; P = 0.085). 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 (OR = 1.857; 95% CI = 1.073-3.214; P = 0.027), whereas >1 year of exposure to ritonavir-boosted lopinavir and ritonavir-boosted darunavir was not.
  
  
  CONCLUSIONS
  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.
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishijima
authors.forename: Takuro
authors.initials: T
authors.lastname: Shimbo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hamada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
mesh_terms: D000005:Abdomen / Q000000981:diagnostic imaging; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D002769:Cholelithiasis / Q000139:chemically induced* / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D015995:Prevalence; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir
keywords: antiretroviral therapy; gallstones; protease inhibitors