Impact of protease inhibitors on the evolution of urinary markers: Subanalyses from an observational cross-sectional study

Medicine (Baltimore). 2016 Aug;95(32):e4507. doi: 10.1097/MD.0000000000004507.

Abstract

Kidney injury (defined as the presence of albuminuria, proteinuria, glycosuria [without hyperglycemia], hematuria, and/or renal hypophosphatemia) is an emerging problem in human immunodeficiency virus (HIV)-infected patients, although few data are available on the role of protease inhibitors (PIs) in this condition.To determine the time to kidney injury in a cohort of HIV-infected patients receiving a PI-containing regimen.We report the results of a subanalysis of a published cross-sectional study. The subanalysis included only patients receiving PI-containing regimens for more than 6 months (377 of the overall 970 patients). We determined associated factors and constructed receiver operating characteristic curves to estimate time to kidney injury depending on the PI used.The percentage of patients with kidney injury was 27.7% for darunavir, 27.9% for lopinavir, and 30% for atazanavir. Time to kidney injury was as follows: 229 days for atazanavir/ritonavir (area under the curve [AUC], 0.639; sensitivity, 0.89; specificity, 0.41); 332 days for atazanavir/ritonavir plus tenofovir (AUC, 0.603; sensitivity, 0.75; and specificity, 0.29); 318 days for nonboosted atazanavir (AUC, 0.581; sensitivity, 0.89; and specificity, 0.29); 478 days for lopinavir/ritonavir (AUC, 0.566; sensitivity, 0.864; and specificity, 0.44); 1339 days for lopinavir/ritonavir plus tenofovir (AUC, 0.667; sensitivity, 0.86; and specificity, 0.77); 283 days for darunavir/ritonavir (AUC, 0.523; sensitivity, 0.80; and specificity, 0.261); and 286 days for darunavir/ritonavir plus tenofovir (AUC, 0.446; sensitivity, 0.789; and specificity, 0.245). The use of lopinavir/ritonavir without tenofovir was a protective factor (odds ratio = 1.772; 95%CI, 1.070-2.93; P = 0.026).For all PIs, the percentage of patients with kidney injury exceeded 27%, irrespective of tenofovir use. The longest time to kidney injury was recorded with lopinavir/ritonavir. These results demonstrate the need for renal monitoring, including urine samples, in patients receiving a PI-based regimen, even when tenofovir is not used concomitantly.

Publication types

  • Observational Study

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / urine
  • Adult
  • Albuminuria / chemically induced
  • Albuminuria / urine
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Atazanavir Sulfate / adverse effects
  • Atazanavir Sulfate / therapeutic use
  • Biomarkers / urine
  • Cross-Sectional Studies
  • Darunavir / administration & dosage
  • Darunavir / therapeutic use
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / urine
  • HIV Protease Inhibitors / adverse effects*
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Lopinavir / adverse effects
  • Lopinavir / therapeutic use
  • Male
  • Middle Aged
  • Proteinuria / chemically induced
  • Proteinuria / urine
  • Ritonavir / adverse effects
  • Ritonavir / therapeutic use

Substances

  • Biomarkers
  • HIV Protease Inhibitors
  • Lopinavir
  • Atazanavir Sulfate
  • Ritonavir
  • Darunavir