Cerebrospinal Fluid Inhibitory Quotients of Antiretroviral Drugs in HIV-Infected Patients Are Associated With Compartmental Viral Control
Cerebrospinal Fluid Inhibitory Quotients of Antiretroviral Drugs in HIV-Infected Patients Are Associated With Compartmental Viral Control
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DOI：
10.1093/cid/ciu773
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发表时间：
2015-01-15
影响因子：
11.8
通讯作者：
Bonora, Stefano
中科院分区：
文献类型：
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作者：
Calcagno, Andrea;Simiele, Marco;Bonora, Stefano
背景。尽管高效抗逆转录病毒治疗（HAART）有效，但大部分人类免疫缺陷病毒（HIV）感染患者可能会出现中度神经认知障碍。抗逆转录病毒药物进入中枢神经系统可能与预防和治疗艾滋病毒相关的神经认知障碍有关；然而，明确的脑脊液（CSF）药效学目标尚不清楚。方法。前瞻性招募接受 HAART 治疗的野生型 HIV 成人。比较不同药物之间的 CSF 浓度（通过质谱法测量）和抑制商（CSF 浓度除以体外 50% 和 95% 抑制浓度），并与 CSF HIV RNA 水平相关。脑脊液逃逸被定义为脑脊液 HIV RNA >50 拷贝/mL，尽管当代血浆 HIV RNA 低于该阈值。结果。 127 名患者（91 名男性 [71.7%]，93 名白人 [73.2%]，中位年龄 46 岁[四分位距，40.5-54.5 岁]）提供了 174 份配对的脑脊液和血浆样本。每日两次达芦那韦、每日一次达芦那韦和依非韦伦具有最高的 CSF 95% 抑制商（分别为 18.5、8.2 和 6.4）。较高的最低 CD4 细胞计数 (P = .01) 和血浆 HIV RNA 1) 对脑脊液逃逸有保护作用 (P = .01)。结论。脑脊液95%抑制商可用于比较抗逆转录病毒药物隔室暴露；他们值得进行纵向研究，以评估接受治疗的 HIV 感染患者脑脊液药物浓度是否充足。
Background. Despite the efficacy of highly active antiretroviral treatment (HAART), a large proportion of human immunodeficiency virus (HIV)-infected patients may develop moderate neurocognitive impairment. Antiretroviral drug passage into the central nervous system may be relevant for preventing and treating HIV-associated neurocognitive disorder; nevertheless, clear cerebrospinal fluid (CSF) pharmacodynamic targets are not known.Methods. HAART-treated adults with wild-type HIV were prospectively enrolled. CSF concentrations (measured by mass spectrophotometric methods) and inhibitory quotients (CSF concentrations divided by in vitro 50% and 95% inhibitory concentrations) were compared among different drugs and related to CSF HIV RNA levels. CSF escape was defined as CSF HIV RNA >50 copies/mL despite contemporary plasma HIV RNA below that threshold.Results. One hundred twenty-seven patients (91 male [71.7%], 93 white [73.2%], with a median age of 46 years [interquartile range, 40.5-54.5 years]) provided 174 paired CSF and plasma samples. Twice-daily darunavir, once-daily darunavir, and efavirenz had the highest CSF 95% inhibitory quotients (18.5, 8.2, and 6.4, respectively). Higher nadir CD4 cell count (P = .01) and plasma HIV RNA 1) was protective for CSF escape (P = .01).Conclusions. Cerebrospinal fluid 95% inhibitory quotients may be used to compare antiretroviral drug compartmental exposure; they deserve longitudinal studies to assess the adequacy of CSF drug concentrations in treated HIVinfected patients.