title: Is ritonavir-boosted atazanavir a risk for cholelithiasis compared to other protease inhibitors?
abstract: OBJECTIVE
  To compare the incidence of complicated cholelithiasis in patients receiving ritonavir-boosted atazanavir (ATV/r)- containing antiretroviral therapy with those on other protease inhibitors (PIs).
  
  
  METHODS
  We conducted a single-center retrospective cohort study of patients who started either ritonavir-boosted ATV/r- or other PIs (ritonavir-boosted fosamprenavir, unboosted fosamprenavir, lopinavir/ritonavir, and ritonavir-boosted darunavir) -containing antiretroviral therapy.
  
  
  METHODS
  The incidence of complicated cholelithiasis was determined in each group. Complicated cholelithiasis was defined as follows: 1) cholelithiasis complicated by cholecystitis, cholangitis, or pancreatitis or 2) symptomatic cholelithiasis or choledocholithiasis which required invasive procedures such as cholecystomy and endoscopic retrograde cholangiopancreatography. The effects of ATV/r were estimated by univariate and multivariate Cox hazards models as the primary exposure.
  
  
  RESULTS
  Complicated cholelithiasis was diagnosed in 3 patients (2.23 per 1000 person-years) in the ATV/r group (n = 466), and 3 (1.64 per 1000 person-years) in the other PIs group (n = 776), respectively. The incidence was not statistically different in the two groups by log-rank test (P = 0.702). By univariate and multivariate analysis adjusted for age and body weight, ATV/r use was not associated with cholelithiasis. (HR = 1.365; 95% CI, 0.275-6.775; p = 0.704) (adjusted HR = 1.390; 95% CI, 0.276-7.017; p = 0.690). For the 3 patients who developed cholelithiasis in the ATV/r group, the time to the diagnosis of cholelithiasis was 18, 34, and 39 months, respectively.
  
  
  CONCLUSIONS
  In this study, the incidence of complicated cholelithiasis was low and was not different between patients on ATV/r and those on other PIs. On the contrary to ATV/r-associated nephrolithiasis, the possible risk of cholelithiasis should not preclude the use of ATV/r.
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hamada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishijima
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.forename: Katsuji
authors.initials: K
authors.lastname: Teruya
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: D000328:Adult; D000069446:Atazanavir Sulfate; D002769:Cholelithiasis / Q000737:chemistry*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects* / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use*; D012189:Retrospective Studies; D019438:Ritonavir / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir