A randomized controlled trial of therapeutic drug monitoring in treatment-naive and -experienced HIV-1-infected patients.
OBJECTIVE
To improve the utility of therapeutic drug monitoring (TDM) by defining the proportion of patients with and predictors of above or below target protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) concentrations.


METHODS
This 48-week, multicenter, open-label clinical trial randomized patients to TDM versus standard of care (SOC). Serial pharmacokinetics, including a week-2 3-sample sparse collection, and expert committee TDM recommendations were given to TDM-arm patients' providers.


RESULTS
Seventy-four (39%) of 190 patients had week-2 concentrations outside of targets and 122 (64%) of 190 had nontarget exposure at least once over 48 weeks. Providers accepted 75% of TDM recommendations. Among patients with below-target concentrations, more TDM-arm than SOC-arm patients achieved targets (65% vs. 45%; P = 0.09). Increased body weight and efavirenz or lopinavir/ritonavir use were significant predictors of nontarget concentrations. Patients at target and patients who achieved targets after TDM-directed dose modifications trended toward greater viral load reductions at week 48 than patients with below-target exposures (HIV RNA reductions: 2.4, 2.3, and 1.9 log10 copies/mL, respectively; P = 0.09).


CONCLUSIONS
Most patients had nontarget PI and/or NNRTI concentrations over 48 weeks. TDM recommendations were well accepted and improved exposure. Patients below TDM targets trended toward worse virologic response.
Best
Brookie M
BM
University of California, San Diego, San Diego, CA 92013, USA. brookie@ucsd.edu
Goicoechea
Miguel
M
Witt
Mallory D
MD
Miller
Loren
L
Daar
Eric S
ES
Diamond
Catherine
C
Tilles
Jeremiah G
JG
Kemper
Carol A
CA
Larsen
Robert
R
Holland
Diane T
DT
Sun
Shelly
S
Jain
Sonia
S
Wagner
Glenn
G
Capparelli
Edmund V
EV
McCutchan
J Allen
JA
Haubrich
Richard H
RH
D000328:Adult; D000465:Algorithms; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D044469:Racial Groups; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics