title: Pharmacologic optimization of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (POPIN)--a randomized controlled trial of therapeutic drug monitoring and adherence support.
abstract: We evaluated the feasibility and effectiveness of therapeutic drug monitoring (TDM) and adherence support (collectively, AT) vs standard of care (SOC) in patients receiving HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) within a nurse-led clinic. Primary end points were failure to achieve viral load of <50 copies/mL at 24 weeks, viral rebound, or development of treatment limiting toxicity. One hundred twenty-two patients (AT 63 and SOC 59) were followed-up every 12 weeks, for a median of 72 weeks. No difference was observed between arms in risk of reaching a study end point or between groups of patients with abnormal vs "therapeutic" drug concentrations. Interindividual variabilities (coefficient of variation) were the following: efavirenz, 77.5%; nevirapine, 74.5%; lopinavir, 73.4%; nelfinavir, 83.7%; indinavir, 80.8%; saquinavir, 112.4%. Intraindividual variabilities (median coefficient of variation) were the following: NNRTIs, approximately 25%; PIs, 48.4%. Despite persistently abnormal results in 26 of patients in the AT arm (38%), dosage adjustment was only undertaken in 9 patients (35%).A significant proportion of patients had drug concentrations outside the therapeutic range. The Pharmacologic Optimization of PIs and NNRTIs (POPIN) study confirms that TDM trials are complex to interpret and statistically underpowered, with effectiveness better assessed through the clinical utility of a TDM result, whether normal or abnormal. Although TDM of PIs and NNRTIs may be useful in selected patients, routine and unselected use is not supported by current evidence.
authors.affiliation: Liverpool HIV Pharmacology Group, Department of Pharmacology, University of Liverpool, UK. khoo@liv.ac.uk
authors.forename: Saye H
authors.initials: SH
authors.lastname: Khoo
authors.forename: Judith
authors.initials: J
authors.lastname: Lloyd
authors.forename: Mark
authors.initials: M
authors.lastname: Dalton
authors.forename: Alec
authors.initials: A
authors.lastname: Bonington
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hart
authors.forename: Sara
authors.initials: S
authors.lastname: Gibbons
authors.forename: Peter
authors.initials: P
authors.lastname: Flegg
authors.forename: John
authors.initials: J
authors.lastname: Sweeney
authors.forename: Edmund G L
authors.initials: EG
authors.lastname: Wilkins
authors.forename: David J
authors.initials: DJ
authors.lastname: Back
mesh_terms: D000328:Adult; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011787:Quality of Health Care / Q000706:statistics & numerical data*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013223:Statistics as Topic; D013997:Time Factors; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors