10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 6-8 November 2008, London, UK

COMPARISON OF DIRECTLY MEASURED AND ESTIMATED GLOMERULAR FILTRATION RATE IN PATIENTS WITH SUPPRESSIVE HAART INCLUDING ZIDOVUDINE, SWITCHING TO TENOFOVIR

Antiviral Therapy 2008; 13(Suppl. 4):A16 (abstract no. O-22)

SME Vrouenraets^1,2, E Fernandez Garcia², FWNM Wit^1,2, K Brinkman³, FJ Hoek¹, RT Krediet¹ and P Reiss^1,2 on behalf of the PREPARE Study Group
¹Academic Medical Center, Amsterdam, the Netherlands; ²IATEC, Amsterdam, the Netherlands; ³Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands

AIM: Tenofovir (TDF) has been associated with nephrotoxicity, including decreased creatinine clearance (CrCl) and proximal tubular dysfunction. However, no studies have directly measured glomerular filtration rate (GFR) prospectively, but all have reported estimated evaluations of kidney function. We investigated the effect of TDF on GFR, measured with both the gold-standard (mGFR) and estimated (eGFR).

METHODS: A subset of 19 patients participating in a randomized trial comparing continued suppressive first-line highly active antiretroviral therapy (HAART) with zidovudine/ lamivudine with switching to TDF/emtricitabine, both plus either a non-nucleoside reverse transcriptase inhibitor or protease inhibitor (PI), were studied. mGFR was determined during continuous infusion of [¹²⁵ I]-iothalamate from timed urine collections and corrected for voiding inaccuracies. eGFR was assessed by Cockcroft–Gault (CG), MDRD (Modification of Diet in Renal Disease), cystatin C and CrCl using plasma and 24 h urine samples.

RESULTS: Of 19 patients, 18 were men, 15 Caucasian, mean (±sd) age 46.0 (8.9) years, body mass index 23.9 (3.0) kg/m², mean HAART duration 5.9 (2.4) years, baseline CD4+ T-cell count 579 (238) cells/mm³ and plasma HIV type-1 RNA<50 copies/ml in all patients. A total of 17 patients were on NNRTI- and two were on boosted PI-containing regimens. After 24 weeks, all patients remained virologically suppressed. The mean mGFRs, eGFRs and change from baseline are shown in Table 1. A significantly greater reduction in mGFR and all eGFRs, except the CrCl and cystatin C-derived eGFR, was observed 24 weeks after switching to TDF compared with the continued zidovudine arm. The mean (accuracy), sd (precision) of the deviations from the mGFR were reasonably good for CG (-2, 23) and CrCl (-3, 26), but MDRD-4 (-42, 29), MDRD-6 (-17, 33) and cystatin C (-44, 30) eGFR underestimated real GFR and performed poorly.

CONCLUSIONS: Mean mGFR decreased by almost 10% at 6 months after switch to tenofovir, therefore routine monitoring of renal function is warranted. In this small subset of patients with preserved renal function and suppressed HIV-infection, CG best reflected measured GFR and might be preferred over other estimates to monitor glomerular function in antiretroviral-treated patients.

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2008-11-06
O-22

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