A randomized controlled trial of therapeutic drug monitoring in treatment-naive and -experienced HIV-1-infected patients

被引:34
作者
Best, Brookie M.
Goicoechea, Miguel
Witt, Mallory D.
Miller, Loren
Daar, Eric S.
Diamond, Catherine
Tilles, Jeremiah G.
Kemper, Carol A.
Larsen, Robert
Holland, Diane T.
Sun, Shelly
Jain, Sonia
Wagner, Glenn
Capparelli, Edmund V.
McCutchan, J. Allen
Haubrich, Richard H.
机构
[1] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Sch Med, Dept Pediat, San Diego, CA 92103 USA
[2] Univ Calif Los Angeles, Med Ctr, Biomed Res Inst, David Geffen Sch Med, Los Angeles, CA USA
[3] Univ Calif Irvine, Irvine, CA USA
[4] Santa Clara Valley Med Ctr, San Jose, CA 95128 USA
[5] Univ So Calif, Los Angeles, CA USA
[6] RAND Corp, Santa Clara, CA USA
关键词
anti-HIV agents; antiretroviral therapy; clinical trials; HIV; drug monitoring; pharmacokinetics;
D O I
10.1097/QAI.0b013e318156f029
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 log(10) 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.
引用
收藏
页码:433 / 442
页数:10
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