Background: This study aimed to evaluate whether low darunavir (DRV) minimum plasma concentration (Cmin) values contribute to virological outcomes during DRV/ritonavir monotherapy (mtDRV/rtv).
Methods: This was a prospective observational single-arm 96-week efficacy study in virologically suppressed subjects on triple therapy switched to mtDRV/rtv (800/100 mg every 24 h). Previous virological failures (VF) on protease-inhibitor-based regimens were allowed if the historical resistance tests showed no major resistance mutation to DRV/rtv. VF was defined as two consecutive HIV RNA measurements of >200 copies/ml. Efficacy was analysed by per-protocol and by intention-to-treat analyses. Plasma DRV Cmin values were measured by LC-MS/MS.
Results: A total of 150 subjects were included. At week 96, the efficacy rate on treatment was 83.6% (95% CI 77.2%, 90.0%) by per-protocol analysis and 67.6% (95% CI 60.0%, 75.2%) by intention-to-treat. In the whole cohort the median (IQR) DRV Cmin was significantly higher during the periods of undetectable than of detectable viraemia (1.82 µg/ml [1.47-2.46] versus 1.56 µg/ml [0.93-2.32]; P=0.006) as well as in the subjects with blips and VF. However, a cutoff point sufficiently sensitive and specific could not be found.
Conclusions: The DRV Cmin values are related to viral control during mtDRV/rtv, but therapeutic drug monitoring cannot be recommended routinely as a precise cutoff point is unknown. Adherence is a key success factor on this regimen.
Trial registration: ClinicalTrials.gov NCT01606722.