"White coat compliance" limits the reliability of therapeutic drug monitoring in HIV-1-infected patients.

PURPOSE: To analyze the extent of improved adherence preceding a clinic visit ("white coat compliance") in a clinical trial and its potential impact on the utility of therapeutic drug monitoring (TDM). METHOD: In this randomized, open-label trial, 190 antiretroviral-naïve, HIV-1-infected subjects received lopinavir/ritonavir capsules, once or twice daily, with tenofovir DF and emtricitabine (both once daily) for 96 weeks. Lopinavir/ritonavir compliance was assessed using MEMS. RESULTS: 178 subjects (107 once daily, 71 twice daily) had plasma samples collected for lopinavir concentration resulting in 768 visits with pharmacokinetic (PK) assessment. The results were not used to provide feedback or recommend dose changes. For 239 (31%) of these visits, drug intake was perfect 1-3 days before PK sampling, whereas compliance during the remainder of the inter-PK visit period was < or = 95%. This phenomenon was noted in 66% of subjects, more frequently among twice-daily than once-daily subjects (85% vs. 54%; p < .0001), and may have led to determination of "therapeutic" drug levels despite overall adherence < or = 95%. The opposite phenomenon (>95% compliance reported during the inter-PK visit period, yet a dose missed the day before PK sampling) was observed for 1% of PK visits and clustered in 5% of subjects. CONCLUSIONS: In a substantial portion of visits and a majority of subjects, a white coat compliance pattern was observed. Drug concentration results obtained at these visits could deliver unreliable estimates of long-term drug exposure.

Decreased adherence to antiretroviral therapy observed prior to transient human immunodeficiency virus type 1 viremia.

BACKGROUND: To identify potential causes and clinical implications of transient increases in plasma viral load (hereafter, "blips"). METHODS: M99-056 and M02-418 were prospective, randomized trials evaluating the safety and efficacy of lopinavir/ritonavir (LPV/r) capsules administered twice per day or once per day to subjects infected with human immunodeficiency virus-1 (HIV-1). Plasma viral load was measured every 4 weeks (from baseline through week 24, excluding week 12 and week 20 in M02-418), every 8 weeks (from week 24 through week 48), and every 12 weeks (from week 48 through week 96). Blips were defined by 1 plasma viral load measurement of between 50-1000 copies/mL, immediately preceded and immediately followed by a measurement of <50 copies/mL. A medication event monitoring system was used to record the date and time subjects administered a dose of LPV/r. RESULTS: Of 228 subject enrolled, event monitor data were available for 223 (98%) subjects (92 of whom received twice-daily LPV/r therapy, and 131 of whom received once-daily therapy). Viral load blips (median plasma viral load, 82 copies/mL [range, 51-858 copies/mL]) were identified in 60 (27%) of the subjects (21 in the LPV/r twice-daily group and 39 in the LPV/r once-daily group). Neither the baseline plasma viral load nor the CD4(+) T cell count were associated with blips. During the week prior to a blip, the mean number of days that the subject administered the prescribed number of doses was lower than the number during a matched period for the same subject during which a blip did not occur (5.55 vs. 6.22 days; P = .007). Blips were not associated with virologic failure or the development of drug resistance. CONCLUSIONS: Blips were associated with decreased adherence, but not with virologic failure or development of drug resistance in these studies of LPV/r. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00043966 .