Chan-Tack, K. M., Truffa, M. M., Struble, K. A. & Birnkrant, D. B. Atazanavir-associated nephrolithiasis: cases from the US Food and Drug Administration's Adverse Event Reporting System. AIDS 21, 1215-1218

Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
AIDS (Impact Factor: 5.55). 06/2007; 21(9):1215-8. DOI: 10.1097/QAD.0b013e32813aee35
Source: PubMed


The risk of nephrolithiasis associated with atazanavir is not well characterized. The US Food and Drug Administration's Adverse Event Reporting System was searched for reports of nephrolithiasis in HIV-infected patients taking an atazanavir-based regimen. Thirty cases were identified. Many patients required hospitalization for management, including lithotripsy, ureteral stent insertion, or endoscopic stone removal. Some cases of nephrolithiasis resulted in atazanavir discontinuation. Healthcare professionals and patients should be informed that nephrolithiasis is a possible adverse event with atazanavir.

3 Reads
  • Source
    • "In model 3, we added variables with P values <0.05 in univariate analysis after adjustment (these included tenofovir use, serum uric acid per 1 mg/dl, and past history of renal stones). Possible risk factors for ATV/r-related nephrolithiasis identified in previous studies were also added to model 3 (these included prior exposure to IDV) [7,8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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). 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.
    Full-text · Article · Oct 2013 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lopinavir/ritonavir has been the recommended boosted protease inhibitor for treatment-naive individuals in all guidelines since its approval in the year 2000. More recently, the rest of ritonavir-boosted protease inhibitors (namely lopinavir once-daily, fosamprenavir, saquinavir, atazanavir, and darunavir) have demonstrated non-inferior antiviral efficacy at 48 weeks than lopinavir twice-daily. Overall, all ritonavir-boosted protease inhibitors display a high genetic and pharmacological barrier to resistance development and protect the rest of the drugs on board in the regimen, achieving similar CD4 count gains among them. During the last year, studies conducted with atazanavir and darunavir have demonstrated superior virologic efficacy against lopinavir at 96 weeks in their pivotal trials. These two protease inhibitors provide significant improvements in triglycerides and gastrointestinal toxicity, together with simpler once-daily formulations, compared to lopinavir. In the case of atazanavir, this is mainly driven by a lower rate of discontinuations due to drug-related side effects, as pure antiviral efficacy is essentially similar to lopinavir. Furthermore, the gastrointestinal intolerance of lopinavir is actually compensated by an increased risk of hyperbilirubinemia and jaundice with atazanavir, but this is more a cosmetic problem and rarely a cause of drug withdrawal. Darunavir has been licensed to be taken once-daily in treatment-naive patients, and shows significantly better lipid and gastrointestinal tolerance than lopinavir. Robust sensitivity analysis with darunavir prove superior antiviral efficacy than lopinavir at 96 weeks also when non-virologic failures (toxicity and discontinuations) are censored, or when only patients receiving lopinavir twice-daily are included in the estimation. Moreover, darunavir has shown superior antiviral efficacy than lopinavir, particularly in three situations of particular clinical concern: high baseline viral load, low baseline CD4 counts, and suboptimal drug adherence. Over the last years, the treatment landscape with ritonavir-boosted protease inhibitors as initial HIV therapy has accomplished significant advances, with improved degrees of efficacy, tolerability, and convenience, that should be used to guide treatment choice in first-line antiretroviral therapy.
    Preview · Article · Oct 2009 · AIDS reviews
  • [Show abstract] [Hide abstract]
    ABSTRACT: With the introduction of highly active antiretroviral therapy, we have witnessed prolonged survival with the potential for normal life expectancy in HIV-infected individuals. With improved survival and increasing age, HIV-infected patients are increasingly likely to experience co-morbidities that affect the general population, including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C, cigarette smoking and injection drug use. Furthermore, they have exposures unique to this population, including antiretrovirals and other medications. Therefore, the differential diagnosis is vast. Early identification (through efficient screening) and definitive diagnosis (by kidney biopsy when indicated) of kidney disease in HIV-infected individuals are critical to optimal management. Earlier interventions with disease-specific therapy, often with the help of a nephrologist, are likely to lead to better outcomes. In those with chronic kidney disease, interventions, such as aggressive blood pressure control with the use of ACE inhibitors or angiotensin receptor antagonists where tolerated, tight blood glucose control in those with diabetes, and avoidance of potentially nephrotoxic medications, can slow progression and prevent end-stage renal disease. Only with greater awareness of kidney-disease manifestations and their implications in this particularly vulnerable population will we be able to achieve success in confronting this growing problem.
    No preview · Article · Feb 2008 · Drugs
Show more