Therapeutic Drug Monitoring
Friday, 1:30 - 3:30 pm
Background: Effective therapeutic drug monitoring for antiretrovirals (ARV) requires a better understanding of intra-individual variability in pharmacokinetics. Frequent repeated sampling of drug concentrations in an individual is usually not possible.
Methods: We determined protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) concentrations in 10 patients with undetectable plasma HIV RNA (< 50 copies/mL) who were stable on their current regimen for at least 3 months. Plasma was collected at the same time of day 3 times every week for as long as 4 months in order to define the frequency of virologic “blips” (isolated plasma HIV RNA ≥ 50 copies/mL). Patients were instructed to take their ARV at the same time every day. Plasma samples for HIV RNA and drug concentration analysis were obtained simultaneously. Plasma PI and NNRTI concentrations were determined using validated HPLC methods. Pharmacokinetic variance was expressed as intra-individual % coefficient of variation (ICV) = SD/mean.
Results: Of 713 samples, blips occurred in 26 (3.6%) but did not coincide with low drug concentrations. ICV% was determined for a total of 17 drugs using 600 samples. ICV% was unexpectedly high in most patients taking PI (lopinavir/ritonavir 24%, 33%, 52%, 85%; nelfinavir/M8 metabolite 30/44%, 38/52%; ritonavir 34%, 43%; saquinavir 52%, 55%). ICV% for NNRTI was lower (efavirenz 7%, 13%, 28%, 51%; nevirapine 26%). Median ICV% for all PI was 43% (n = 12) and for all NNRTI was 26% (n = 5). Quality controls excluded laboratory artifact as a likely contributor to variance.
Conclusions: Using validated HPLC methods, intraindividual variance in the concentration of ARV was surprisingly high in virologically suppressed patients. Possible contributors include food effects, concomitant use of prescription and herbal medications, or medication timing, which was assessed by self-report. High intraindividual pharmacokinetic variability may limit the utility of therapeutic drug monitoring for some ARV in some settings.
Keywords: therapeutic drug monitoring; antiretrovirals; blips