Ritonavir-boosted darunavir is rarely associated with nephrolithiasis compared with ritonavir-boosted atazanavir in HIV-infected patients

PLoS One. 2013 Oct 10;8(10):e77268. doi: 10.1371/journal.pone.0077268. eCollection 2013.

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).

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects*
  • Atazanavir Sulfate
  • Darunavir
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Humans
  • Male
  • Middle Aged
  • Nephrolithiasis / chemically induced*
  • Nephrolithiasis / epidemiology
  • Oligopeptides / administration & dosage
  • Oligopeptides / adverse effects*
  • Proportional Hazards Models
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Retrospective Studies
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects*
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects*

Substances

  • Anti-HIV Agents
  • Oligopeptides
  • Pyridines
  • Sulfonamides
  • Atazanavir Sulfate
  • Ritonavir
  • Darunavir

Grants and funding

This work was supported by a Grant-in-Aid for AIDS research from the Ministry of Health, Labor, and Welfare, Japan (H22-AIDS-001), and the Global Center of Excellence Program, the Ministry of Education, Science, Sports and Culture of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.