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.