title: Tenofovir plasma concentrations according to companion drugs: a cross-sectional study of HIV-positive patients with normal renal function.
abstract: As the risk of tenofovir-associated renal toxicity has been found to be proportional to the drug plasma concentration, our aim was to measure the determinants of tenofovir plasma exposure in HIV-positive patients with normal renal function. A cross-sectional analysis was conducted in HIV-positive patients chronically receiving tenofovir-containing highly active antiretroviral therapies (HAARTs). Patients on tenofovir-containing antiretroviral regimens, presenting 22 to 26 h after drug intake, having estimated glomerular filtration rates above 60 ml/min, reporting high adherence to antiretroviral medications (above 95% of the doses), and signing a written informed consent were included. Plasma tenofovir concentrations were measured through a validated high-performance liquid chromatography-mass spectrometry (HPLC/LC-MS) method. The tenofovir trough concentrations in 195 patients (median, 50 ng/ml, and interquartile range, 35 to 77 ng/ml) were significantly associated with the estimated glomerular filtration rate, body mass index, and third-drug class (protease-containing versus protease-sparing regimens) (with the highest exposure in unboosted-atazanavir recipients). The results of multivariate analysis showed that the third-drug class and the weight/creatinine ratio were independent predictors of tenofovir trough concentrations. This cross-sectional study shows that tenofovir trough concentrations are predicted by the weight/creatinine ratio and by the coadministered antiretrovirals, with protease inhibitors (whether boosted or unboosted) being associated with the highest plasma exposure. These data, previously available in healthy subjects or for some drugs only, could be useful for designing strategies to manage tenofovir-associated toxicity, since this toxicity has been reported to be dose dependent.
authors: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors: A
authors: A
authors: Calcagno
authors: D
authors: D
authors: Gonzalez de Requena
authors: M
authors: M
authors: Simiele
authors: A
authors: A
authors: D'Avolio
authors: M C
authors: MC
authors: Tettoni
authors: B
authors: B
authors: Salassa
authors: G
authors: G
authors: Orofino
authors: C
authors: C
authors: Bramato
authors: V
authors: V
authors: Libanore
authors: I
authors: I
authors: Motta
authors: P
authors: P
authors: Bigliano
authors: E
authors: E
authors: Orsucci
authors: G
authors: G
authors: Di Perri
authors: S
authors: S
authors: Bonora
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D063065:Organophosphonates / Q000097:blood* / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir
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