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A Randomized, Pilot Trial to Evaluate Glomerular Filtration Rate by Creatinine or Cystatin C in Naive HIV-Infected Patients After Tenofovir/Emtricitabine in Combination With Atazanavir/Ritonavir or Efavirenz

Albini, Laura MSc*; Cesana, Bruno Mario MD; Motta, Davide MD*; Focà, Emanuele MD*; Gotti, Daria MSc*; Calabresi, Alessandra MD*; Izzo, Ilaria MD*; Bellagamba, Rita MD; Fezza, Rita MD; Narciso, Pasquale MD; Sighinolfi, Laura MD§; Maggi, Paolo MD||; Quiros-Roldan, Eugenia MD, PhD*; Manili, Luigi MD; Guaraldi, Giovanni MD#; Lapadula, Giuseppe MD**; Torti, Carlo MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: January 1st, 2012 - Volume 59 - Issue 1 - p 18–24
doi: 10.1097/QAI.0b013e31823a6124
Clinical Science

Background Glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on creatinine or cystatine C may be more accurate methods especially in patients without chronic kidney disease. There is lack of data on GFR estimated by these methods in patients on highly active antiretroviral therapy.

Methods Antiretroviral-naive HIV-infected patients were randomized to tenofovir/emtricitabine in association with atazanavir/ritonavir (ATV/r) or efavirenz (EFV) Patients had to have an actual creatinine clearance >50 mL/minute (24-hour urine collection) and were followed for 48 weeks.

Results Ninety-one patients (48 ATV/r, 43 EFV) were recruited. Using the CKD-EPI creatinine formula, there was a significant decrease in GFR up to week 48 in patients receiving ATV/r (4.9 mL/minute/m2, P = 0.02) compared with a not statistically significant increment in patients prescribed EFV. Using the cystatin C–based equation, we found greater decrease in GFR in both arms, although, in the EFV arm, the decrease was not statistically significant (5.8 mL/minute/m2, P = 0.92). At multivariable analysis, ATV/r was a significant predictor of greater decrease in estimated glomerular filtration rate (eGFR) (P = 0.0046) only with CKD-EPI creatinine.

Conclusions ATV/r plus tenofovir caused greater GFR decreases compared with EFV. The evaluation of eGFR by cystatin C confirmed this result, but this method seemed to be more stringent, probably precluding the possibility to detect a significant difference in the pattern of eGFR evolution between the two arms over time. More studies are needed to understand the clinical relevance of these alterations and whether cystatin C is a more appropriate method for monitoring GFR in clinical practice.

*Department of Materno Infantile e Tecnologie Biomediche, Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy

Department of Scienze Biomediche e Biotecnologie, Institute of Statistics in Medicine, University of Brescia, Brescia, Italy

National Institute of Infectious Diseases, I.N.M.I. Lazzaro Spallanzani, Rome, Italy

§Azienda Ospedialiero-Universitaria of Ferrara, department of Infectious Diseases, Sant'Anna Hospital, Ferrara, Italy

||Operative Unit of Infectious Disease, Policlinico di Bari and Ospedale Gionvanni XXIII, Bari, Italy

Department of Nephrology, Spedali Civili di Brescia, Brescia, Italy

#Department of Medicine e Specialitá Mediche, Institute of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy

**Institute of Infectious Diseases, San Gerardo Hospital, Monza, Italy.

Correspondence to: Carlo Torti, MD, Institute of Infectious and Tropical Diseases, University of Brescia, School of Medicine, P.le Spedali Civili, 1, 25123 Brescia, Italy (e-mail:

Dr C.T. and Dr. E.F. have received unrestricted educational grants (as speakers or for participation to conferences) from Abbott, Gilead, Merck, GSK, BMS, Schering Plough, and Roche. The other authors declare no competing interests.

This is a investigator-driven trial conducted without grants from pharmaceutical Companies and none of the authors has a financial or beneficial interest in the products or concepts mentioned in the present article or in competing products that might bias his/her judgment. None of them is in association with any organization that could pose a conflict of interest for the contents of the article.

This clinical trial was registered with EudraCT number 2007-007934-21.

Received June 28, 2011

Accepted September 28, 2011

© 2012 Lippincott Williams & Wilkins, Inc.