Abstract
BackgroundAlthough 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.MethodsIn 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.ResultsRenal 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).ConclusionThe 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.
Highlights
Ritonavir-boosted darunavir (DRV/r) and ritonavir-boosted atazanavir (ATV/r) are the only two protease inhibitors (PI) selected as the preferred choices in the American Department of Health and Human Services (DHHS) guidelines for the initial treatment of patients infected with human immunodeficiency virus-1 (HIV-1)
We recently reported in a single center cohort study that the incidence of renal stones is approximately 10 times higher among patients on ATV/r-containing antiretroviral therapy (ART) than those on other PIs-containing ART [9]
Our study on the effects of ART on renal stone formation included only a small number of patients on DRV/r-containing ART [9,10], and no data are available at present on the incidence of nephrolithiasis in patients treated with DRV/r
Summary
Ritonavir-boosted darunavir (DRV/r) and ritonavir-boosted atazanavir (ATV/r) are the only two protease inhibitors (PI) selected as the preferred choices in the American Department of Health and Human Services (DHHS) guidelines for the initial treatment of patients infected with human immunodeficiency virus-1 (HIV-1) (http://www.aidsinfo.nih.gov/ContentFiles/ AdultandAdolescentGL.pdf). Both drugs are widely used in combination with other antiretroviral drugs, based on their high efficacy, tolerability, favorable lipid profile, and once-daily dosing [1,2,3,4]. 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
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