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and Hepatitis.com Coverage of the
17th Conference on Retroviruses and
Opportunistic Infections (CROI 2010)
February 16 - 19, San Franciso, California
Chronic Kidney Disease Linked to Tenofovir (Viread) in EuroSIDA Study
EuroSIDA is an ongoing observational study that now includes more than 16,500 HIV positive participants at 103 centres in Europe. In the present study, investigators analyzed data from 6843 participants who had at least 3 available serum creatinine measurements.
Most participants (75%) were men, 85% were white, and the median age was 43 years. About 23% were coinfected with hepatitis C virus (HCV), 22% had high blood pressure, and 5% had diabetes all known risk factors for kidney disease. The current median CD4 cell count was relatively high at 450 cells/mm3, but about one-third had a prior AIDS diagnosis.
Participants were followed for an average of about 4 years, accumulating a total 21,482 person-years of data. The researchers looked at rates and risk factors for chronic kidney disease. Confirmed chronic kidney disease was defined as persistent (2 assessments at least 3 months apart) estimated GFR (eGFR) 60 ml/min/1.73m2 if the baseline level was above 60, or a 25% decline if it started lower (Cockcroft-Gault formula). GFR is a measure of how efficiently capillary bundles in the kidney (glomeruli) can filter the blood; creatinine levels are used in the estimation equation.
the influence of antiretroviral agents, drug exposure duration was divided
into 4 categories: never used, used 0-1 years, use 1-2 years, used 2-3
years, and used more than 3 years. The analysis did not include the
mostly recently approved drugs due to insufficient data.
Based on these findings, the researchers summarized, "Increasing exposure to tenofovir [was] associated with a higher risk of chronic kidney disease. Association with chronic kidney disease [was] also identified for indinavir and atazanavir. Results for lopinavir/ritonavir [were] less clear."
The researchers noted that long-term kidney impairment may be due to differing mechanisms including glomerular and tubular dysfunction for tenofovir and build-up of drug crystals or kidney stones for the protease inhibitors.
"We have identified several [antiretrovirals] associated with progressive, long-term renal impairment/chronic kidney disease," they included. "Although biologically plausible, the exact pathogenesis behind these findings remains to be elucidated...Studies on the clinical implications of the findings and the long-term consequences are warranted."
Copenhagen HIV Prgm, Univ of Copenhagen, Denmark; Royal Free and Univ Coll London Med Sch, UK; Academic Med Ctr, Univ of Amsterdam, Netherlands; Ctr Hosp Univ Saint-Pierre, Brussels, Belgium; Charles Univ Hosp, Plzen, Czech Republic; Specialistic Hosp, Chorzow, Poland; Hosp Clin, Barcelona, Spain; Univ Hosp Zurich, Switzerland; Rigshospitalet, Copenhagen, Denmark