title: Ritonavir-boosted darunavir is rarely associated with nephrolithiasis compared with ritonavir-boosted atazanavir in HIV-infected patients.
abstract: BACKGROUND
  Although ritonavir-boosted atazanavir (ATV/r) is known to be associated with nephrolithiasis, little is known about the incidence of nephrolithiasis in patients treated with ritonavir-boosted Darunavir (DRV/r), the other preferred protease inhibitor.
  
  
  METHODS
  In a single-center cohort, the incidence of nephrolithiasis was compared between HIV-infected patients who commenced DRV/r-containing antiretroviral therapy and those on ATV/r. The effects of ATV/r use over DRV/r were estimated by univariate and multivariate Cox hazards models.
  
  
  RESULTS
  Renal stones were diagnosed in only one patient (0.86 per 1000 person-years) of the DRV/r group (n=540) and 37 (20.2 per 1000 person-years) of the ATV/r group (n=517). The median [interquartile (IQR)] observation period in the DRV/r group was 27.1 months (IQR 18.1-38.4 months), and 40.6 months (IQR 17.5-42.7) for the ATV/r group. The total observation period was 1,163.6 person-years and 1,829.6 person-years for the DRV/r group and for the ATV/r group, respectively. In the 37 patients on ATV/r who developed nephrolithiasis, the median time from commencement of ATV/r to diagnosis was 28.1 months (IQR 18.4-42.7), whereas nephrolithiasis in the single patient of the DRV/r group occurred 11.2 month after the introduction of DRV/r. ATV/r use over DRV/r was significantly associated with nephrolithiasis by uni- and multivariate analyses (HR=26.01; 95% CI, 3.541-191.0; p=0.001) (adjusted HR=21.47; 95% CI, 2.879-160.2; p=0.003).
  
  
  CONCLUSIONS
  The incidence of nephrolithiasis was substantially lower in patients on DRV/r than those on ATV/r. The results suggest that DRV/r should be selected for treatment of HIV-infected patients at risk of chronic kidney disease.
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan ; Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishijima
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hamada
authors.forename: Koji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.forename: Ei
authors.initials: E
authors.lastname: Kinai
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Tsukada
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; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000069446:Atazanavir Sulfate; D000069454:Darunavir; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D053040:Nephrolithiasis / Q000139:chemically induced* / Q000453:epidemiology; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects*; D016016:Proportional Hazards Models; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D013449:Sulfonamides; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D000069454:Darunavir