TY - JOUR
T1 - Therapeutic monitoring and variability of Atazanavir in HIV-infected patients, with and without HCV coinfection, receiving boosted or unboosted regimens
AU - Regazzi, Mario
AU - Villani, Paola
AU - Gulminetti, Roberto
AU - Cusato, Maria
AU - Brandolini, Michela
AU - Tinelli, Carmine
AU - Barassi, Alessandra
AU - Maserati, Renato
AU - Sighinolfi, Laura
AU - D'Arminio Monforte, Antonella
AU - Melzi D'Eril, Gian Vico
PY - 2011/6
Y1 - 2011/6
N2 - Background: Adequate plasma trough concentrations (C trough) of protease inhibitors are required to maintain antiviral activity throughout the dosing interval. Therapeutic drug monitoring is used in clinical practice to optimize dosage and avoid toxic or subtherapeutic drug exposure. The pharmacokinetic variability of Atazanavir (ATV) can be relatively large, as a result of several factors. One of the affecting factors may be hepatic impairment due to hepatitis C virus (HCV) coinfection. Methods: We collected trough plasma samples from human immunodeficiency virus (HIV)-1-infected outpatients, with and without HCV coinfection and/or cirrhosis, receiving stable highly active antiretroviral therapy containing ATV. In the total population, we mainly compared the 2 regimens, 300ATV + 100RTV OD [ritonavir (RTV), once daily (OD)] versus 400ATV OD. We used a threshold value of 0.15 mg/mL, based on the proposed therapeutic range (0.15-0.85 mg/mL). Plasma concentrations of ATV were determined by a validated assay using high-performance liquid chromatography with ultraviolet detection. A total of 214 HIV-infected outpatients were included. For each regimen, we compared 3 groups of subjects HIV+/HCV2, HIV+/HCV+, and HIV+/HCV+ with cirrhosis. Results: In the whole study population, we observed a large variability and found suboptimal C trough levels (<0.15 μg/mL) in 23 subjects (2 belonging to the 300/100 OD group and 21 to the 400 OD group). For the standard dosage regimen of 300ATV + 100RTV OD, we did not find a statistical difference between HIV-infected patients without HCV coinfection versus HIV-infected patients with HCV coinfection median 0.85 (interquartile range 0.53-1.34) and 0.95 (0.70-1.36) mg/mL, respectively. In HIV+/HCV+-infected patients with cirrhosis, we found a median C troughof 0.70 (0.43-1.0) μg/mL, with no statistical difference when compared with HIV+/HCV2 infected patients. For the 400ATVOD (n = 90) dosage regimen, the total median ATV C trough was 0.40 (0.23-1.0) μg/mL. In this group, we found a statistically significant difference between HIV+/HCV2 and HIV+/HCV+-infected patients median C trough was 0.23 (0.11-0.42) and 0.52 (0.20-1.0) mg/mL, respectively. In HIV+/HCV+ subjects with cirrhosis, the C trough median value was 0.42 (0.13-0.75) μg/mL, and there was a significant difference when compared with HIV patients without coinfection. Conclusions: Therapeutic drug monitoring of ATV in patients receiving unboosted regimen may be useful to identify those HIVinfected subjects, with or without HCV coinfection, who may benefit from adding low RTV doses, or the subset of patients in whom removal of RTV could be attempted without the risk of suboptimal plasma ATV exposure.
AB - Background: Adequate plasma trough concentrations (C trough) of protease inhibitors are required to maintain antiviral activity throughout the dosing interval. Therapeutic drug monitoring is used in clinical practice to optimize dosage and avoid toxic or subtherapeutic drug exposure. The pharmacokinetic variability of Atazanavir (ATV) can be relatively large, as a result of several factors. One of the affecting factors may be hepatic impairment due to hepatitis C virus (HCV) coinfection. Methods: We collected trough plasma samples from human immunodeficiency virus (HIV)-1-infected outpatients, with and without HCV coinfection and/or cirrhosis, receiving stable highly active antiretroviral therapy containing ATV. In the total population, we mainly compared the 2 regimens, 300ATV + 100RTV OD [ritonavir (RTV), once daily (OD)] versus 400ATV OD. We used a threshold value of 0.15 mg/mL, based on the proposed therapeutic range (0.15-0.85 mg/mL). Plasma concentrations of ATV were determined by a validated assay using high-performance liquid chromatography with ultraviolet detection. A total of 214 HIV-infected outpatients were included. For each regimen, we compared 3 groups of subjects HIV+/HCV2, HIV+/HCV+, and HIV+/HCV+ with cirrhosis. Results: In the whole study population, we observed a large variability and found suboptimal C trough levels (<0.15 μg/mL) in 23 subjects (2 belonging to the 300/100 OD group and 21 to the 400 OD group). For the standard dosage regimen of 300ATV + 100RTV OD, we did not find a statistical difference between HIV-infected patients without HCV coinfection versus HIV-infected patients with HCV coinfection median 0.85 (interquartile range 0.53-1.34) and 0.95 (0.70-1.36) mg/mL, respectively. In HIV+/HCV+-infected patients with cirrhosis, we found a median C troughof 0.70 (0.43-1.0) μg/mL, with no statistical difference when compared with HIV+/HCV2 infected patients. For the 400ATVOD (n = 90) dosage regimen, the total median ATV C trough was 0.40 (0.23-1.0) μg/mL. In this group, we found a statistically significant difference between HIV+/HCV2 and HIV+/HCV+-infected patients median C trough was 0.23 (0.11-0.42) and 0.52 (0.20-1.0) mg/mL, respectively. In HIV+/HCV+ subjects with cirrhosis, the C trough median value was 0.42 (0.13-0.75) μg/mL, and there was a significant difference when compared with HIV patients without coinfection. Conclusions: Therapeutic drug monitoring of ATV in patients receiving unboosted regimen may be useful to identify those HIVinfected subjects, with or without HCV coinfection, who may benefit from adding low RTV doses, or the subset of patients in whom removal of RTV could be attempted without the risk of suboptimal plasma ATV exposure.
KW - Atazanavir
KW - HCV coinfection
KW - HIV
KW - Therapeutic drug monitoring
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U2 - 10.1097/FTD.0b013e31821c2772
DO - 10.1097/FTD.0b013e31821c2772
M3 - Article
C2 - 21544015
AN - SCOPUS:80051788651
VL - 33
SP - 303
EP - 308
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
SN - 0163-4356
IS - 3
ER -