icon-    folder.gif   Conference Reports for NATAP  
  17th CROI
Conference on Retroviruses
and Opportunistic Infections
San Francisco CA
February 16-19, 2010
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Chronic Kidney Disease and Exposure to ART in a Large Cohort with Long-term Follow-up: The EuroSIDA Study - abstract 107LB
  Reported by Jules Levin
CROI Feb 16-19 2010 SF
Ole Kirk*1, A Mocroft2, P Reiss3, S De Wit4, D Sedlacek5, M Beniowski6, J Gatell7, A Phillips2, B Ledergerber8, J Lundgren1,9, and for the EuroSIDA Study Group 1Copenhagen HIV Prgm, Univ of Copenhagen, Denmark; 2Royal Free and Univ Coll London Med Sch, UK; 3Academic Med Ctr, Univ of Amsterdam, The Netherlands; 4Ctr Hosp Univ Saint-Pierre, Brussels, Belgium; 5Charles Univ Hosp, Plzen, Czech Republic; 6Specialistic Hosp, Chorzow, Poland; 7Hosp Clin, Barcelona, Spain; 8Univ Hosp Zurich, Switzerland; and 9Rigshospitalet, Copenhagen, Denmark
Background: Renal impairment in HIV+ persons might be caused by traditional and HIV-related factors; impact of longer-term exposure to specific ART remains poorly elucidated.
Methods: HIV+ persons with ≥3 serum creatinine measurements and corresponding body weight measurements from 2004 onwards were included. Chronic kidney disease (CKD) was defined as either confirmed measurements ≥3 months apart, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 for persons with eGFR >60 at baseline; or confirmed 25% decline in eGFR for persons with eGFR ≥60 at baseline, using the Cockcroft-Gault formula. Poisson regression was used to determine factors (including ART) associated with chronic kidney disease.
Results: During 21,482 person-years of follow-up (median 3.7 [IQR 2.8 to 5.7]) in 6843 persons, 225 (3.3%) progressed to chronic kidney disease, incidence 1.1/100 person-years of follow-up (95%CI 0.9 to 1.2). Using the first definition, 203 patients (90.2%) developed chronic kidney disease, and 150 of these progressed with >10 mL/min/1.73 m2 decline in eGFR. The incidence of CDK increased from 0.7/100 person-years of follow-up (0.5 to 0.8) in persons never exposed to tenofovir (TDF) to 2.4 (1.7 to 3.0) with ≥4 years exposure; for indinavir (IDV), corresponding figures were 0.6 (0.5 to 0.7) and 1.9 (1.4 to 2.3), for atazanavir (ATV) 0.8 (0.7 to 1.0) and 3.9 (2.2 to 5.5), and for lopinavir (LPV) 0.9 (0.7 to 1.1) and 1.8 (1.3 to 2.3). Increasing cumulative exposure of TDF, IDV, ATV, and LPV were associated with a significantly increased rate of CDK(see the table), whereas use of other ART was not. Consistent results were observed in a range of sensitivity analyses and when using the modification of diet in renal disease (MDRD) formulae for eGFR, although of marginal statistical significance for LPV. Among 1558 persons who started TDF, older age, hypertension, hepatitis C co-infection, lower baseline eGFR, and CD4 count were independently associated with increased risk of chronic kidney disease, as was cumulative exposure to TDF, LPV, and ATV.
Conclusions: In this non-randomized, but well-described, large cohort, increasing exposure to TDF was associated with a higher risk of CDK independently of other ART and traditional CKD risk factors. The risk was cumulative for TDF exposure within a follow-up period of 3 to 4 years. The increase in risk of CKD was also true for IDV and ATV, likely reflecting high renal excretion rates for these particular protease inhibitors, while the results for LPV were less clear. Persons who start TDF with a low eGFR and with traditional risk factors for CKD were at greatest risk of CKD.