title: Assessing the impact of substance use and hepatitis coinfection on atazanavir and lopinavir trough concentrations in HIV-infected patients during therapeutic drug monitoring.
abstract: Atazanavir (ATV) and lopinavir (LPV) are widely used HIV-1 protease inhibitors. Like with other protease inhibitors, careful monitoring of potential drug-drug and drug-disease interactions in clinical practice is necessary. The aim of this study was to assess the impact of substance use and hepatitis virus coinfection on plasma ATV and LPV trough concentrations in HIV-positive substance users and nonusers. Individuals established on ATV (300 mg and 100 mg ritonavir daily) or LPV (400 mg and 100 mg ritonavir twice daily)-containing regimens completed two clinical visits (trough and directly observed therapy) during which dosing characteristics, concomitant medication, and substance use were recorded. Trough plasma concentrations (22-26 hours for ATV and 10-14 hours for LPV) were measured using LCMSMS. The influence of substance use was evaluated by Kruskal-Wallis test. Substance use was associated with a marked decrease in trough LPV concentrations during the trough visit (median, 5.536 and 3.791 microg/mL for nonsubstance users and substance users, respectively, P = 0.029). Significantly lower LPV trough levels were also noted among patients with active hepatitis C virus coinfection evaluated as an independent variable (median, 2.253 and 5.927 microg/mL for active and inactive/no hepatitis C virus infection, respectively, P = 0.032). Substance use and hepatitis virus coinfection had limited effects on ATV trough levels. In this cohort, despite the wide interindividual variability of ATV and LPV trough concentrations, significant associations between substance use and active hepatitis C virus infection and low LPV trough concentrations were observed. Further work is needed to assess the optimal dosing regimen when using LPV in HIV-infected substance users.
authors: Pharmacotherapy Research Center, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Amherst, New York 14260, USA.
authors: Judianne
authors: J
authors: Slish
authors: Qing
authors: Q
authors: Ma
authors: Barry S
authors: BS
authors: Zingman
authors: Richard C
authors: RC
authors: Reichman
authors: Margaret A
authors: MA
authors: Fischl
authors: Barbara
authors: B
authors: Gripshover
authors: Alan
authors: A
authors: Forrest
authors: Dan
authors: D
authors: Brazeau
authors: Naomi S
authors: NS
authors: Boston
authors: Linda
authors: L
authors: Catanzaro
authors: Robin
authors: R
authors: DiFrancesco
authors: Gene D
authors: GD
authors: Morse
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D006526:Hepatitis C / Q000097:blood / Q000150:complications*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D019966:Substance-Related Disorders / Q000097:blood / Q000150:complications*; D014481:United States
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate