OASIS

Presentation Abstract

Session Number:

103

Monday, Sep 10, 2012, 11:15 AM - 1:15 PM

Presentation Title:

H-889 - High ATZ and DRV Urine Concentrations and Cristalluria in Asymptomatic Patients Receiving ATV and DRV-Based Regimens

Location:

Halls A-C

Presentation Number:

H-889

Pres. Time:

Monday, Sep 10, 2012, 11:15 AM - 1:15 PM

Category:

Keywords:

atazanavir; renal impairment; darunavir

Author(s):

V. de Lastours, MD - R¹, E. Silva, MD - R ¹, M. Daudon, MD - Pr ², R. Porcher, PhD - R ¹, H. Sauvageon, Pharm - R ¹, J. Molina, MD,PhD - Pr ¹;
¹Saint-Louis Hosp., Paris, France, ²Tenon Hosp., Paris, France.

Financial Disclosures:

V. de Lastours, None..
E. Silva, None..
M. Daudon, None..
R. Porcher, None..
H. Sauvageon, None..
J. Molina, None.

Abstract:

Background: Atazanavir (ATV), an HIV protease inhibitor (PI), has been associated with kidney stones and renal failure. To understand why ATV and not other PIs are responsible for these events, we measured urine and plasma concentrations of recent PIs and searched for PI-crystals in the urine of asymptomatic patients. Methods: Patients on stable antiretroviral including boosted 300mg/d ATV (ATV300/r), unboosted ATV 400mg/d (ATV400), boosted 800mg/d and 1200mg/d DRV (DRV800/r and DRV1200/r), and boosted lopinavir 800mg/d (LPV/r) were evaluated. Plasma and urine were collected simultaneously. PI concentrations were measured with high performance liquid chromatography and spectrophotometric detection. Crystals were detected in fresh urine by polarized microscopy and identified according to their infrared spectrum. Results: PI dosage was performed in 266 patients and crystals were searched in 139 of them. Mean age was 46 years [range 21-74]; 80% were male. Mean duration of HIV infection was 10 years [0.5-29] and current PI regimen had been stable for 22 months [3-129]. Mean CD4-cell counts was 503/mm3; 74% had a HIV-RNA<400 copies/ml. Results from PI dosage are in Table. ATV, boosted or not, as well as DRV concentrated significantly more in urine than LPV (both p<0.0001). ATV-crystals were found in the urine of 7/58 patients under ATZ300/r (12%) and DRV-crystals in 4/51 patients receiving DRV/r (8%). No crystals were found in the 20 patients tested under ATZ400 or the 10 patients under LPV. Conclusions: Unlike LPV, boosted ATV and DRV reached high concentrations in urine and were associated with the detection of crystals. Attention should be paid towards the potential risk of renal colic with both PI.

Mean plasma and urine concentrations according to PI regimen.
	n=	Mean plasma concentration; mg/l (SD)	Mean Urine concentration; mg/l (SD)
ATV400	28	1.3 (2.5)	16.2 (16.3)
ATZ300/r	84	2.3 (5.7)	30 (25)
DRV800/r	98	2.6 (2.1)	33 (26)
DRV1200/r	25	3.7 (3.1)	46.3 (45)
LPV/r	31	6.5 (6.1)	6.7 (5.1)


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