Vinnard Christopher, Manley Isabel, Scott Brittney, Bernui Mariana, Adams Joella, Varghese Sheryl, Zentner Isaac, Kutzler Michele A
Public Health Research Institute, Rutgers, The State University of New Jersey, Newark, NJ, USA.
Division of Infectious Diseases & HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA.
Tuberc Res Treat. 2017;2017:2140974. doi: 10.1155/2017/2140974. Epub 2017 Dec 21.
Rifampin malabsorption is frequently observed in tuberculosis patients coinfected with human immunodeficiency virus (HIV) but cannot be predicted by patient factors such as CD4+ T cell count or HIV viral load.
We sought to describe the relationship between HIV-associated immune activation, measures of gut absorptive capacity and permeability, and rifampin pharmacokinetic parameters in a pilot study of 6 HIV-infected, tuberculosis-uninfected patients who were naïve to antiretroviral therapy.
The median rifampin area under the concentration-versus-time curve during the 8-hour observation period was 42.8 mg·hr/L (range: 21.2 to 57.6), with a median peak concentration of 10.1 mg/L (range: 5.3 to 12.5). We observed delayed rifampin absorption, with a time to maximum concentration greater than 2 hours, in 2 of 6 participants. There was a trend towards increased plasma concentrations of sCD14, a marker of monocyte activation in response to bacterial translocation, among participants with delayed rifampin absorption compared to participants with rapid absorption ( = 0.06).
Delayed rifampin absorption may be associated with elevated markers of bacterial translocation among HIV-infected individuals naïve to antiretroviral therapy. This trial is registered with NCT01845298.
在合并感染人类免疫缺陷病毒(HIV)的结核病患者中,经常观察到利福平吸收不良,但无法通过患者因素(如CD4 + T细胞计数或HIV病毒载量)进行预测。
在一项针对6名未接受过抗逆转录病毒治疗的HIV感染且未感染结核病患者的初步研究中,我们试图描述HIV相关免疫激活、肠道吸收能力和通透性指标与利福平药代动力学参数之间的关系。
在8小时观察期内,利福平浓度-时间曲线下面积的中位数为42.8 mg·hr/L(范围:21.2至57.6),峰值浓度中位数为10.1 mg/L(范围:5.3至12.5)。我们观察到6名参与者中有2名利福平吸收延迟,达峰时间大于2小时。与吸收迅速的参与者相比,利福平吸收延迟的参与者中,sCD14(一种响应细菌易位的单核细胞激活标志物)的血浆浓度有升高趋势(P = 0.06)。
在未接受过抗逆转录病毒治疗的HIV感染者中,利福平吸收延迟可能与细菌易位标志物升高有关。该试验已在ClinicalTrials.gov注册,注册号为NCT01845298。