HIV Neurobehavioral Research Center, University of California-San Diego, 220 Dickinson, Suite B, #8208, San Diego, CA 92103, USA.
Antimicrob Agents Chemother. 2010 Dec;54(12):5156-60. doi: 10.1128/AAC.00507-10. Epub 2010 Sep 27.
HIV-associated neurocognitive disorders continue to be common. Antiretrovirals that achieve higher concentrations in cerebrospinal fluid (CSF) are associated with better control of HIV and improved cognition. The objective of this study was to measure total raltegravir (RAL) concentrations in CSF and to compare them with matched concentrations in plasma and in vitro inhibitory concentrations. Eighteen subjects with HIV-1 infection were enrolled based on the use of RAL-containing regimens and the availability of CSF and matched plasma samples. RAL was measured in 21 CSF and plasma pairs by liquid chromatography-tandem mass spectrometry, and HIV RNA was detected by reverse transcription-PCR (RT-PCR). RAL concentrations were compared to the 50% inhibitory concentration (IC(50)) for wild-type HIV-1 (3.2 ng/ml). Volunteers were predominantly middle-aged white men with AIDS and without hepatitis C virus (HCV) coinfection. The median concurrent CD4(+) cell count was 276/μl, and 28% of CD4(+) cell counts were below 200/μl. HIV RNA was detectable in 38% of plasma specimens and 4% of CSF specimens. RAL was present in all CSF specimens, with a median total concentration of 14.5 ng/ml. The median concentration in plasma was 260.9 ng/ml, with a median CSF-to-plasma ratio of 0.058. Concentrations in CSF correlated with those in with plasma (r(2), 0.24; P, 0.02) but not with the postdose sampling time (P, >0.50). RAL concentrations in CSF exceeded the IC(50) for wild-type HIV in all specimens by a median of 4.5-fold. RAL is present in CSF and reaches sufficiently high concentrations to inhibit wild-type HIV in all individuals. As a component of effective antiretroviral regimens or as the main antiretroviral, RAL likely contributes to the control of HIV replication in the nervous system.
HIV 相关的神经认知障碍仍然很常见。能在脑脊液（CSF）中达到更高浓度的抗逆转录病毒药物与更好的 HIV 控制和改善认知有关。本研究的目的是测量 CSF 中的总拉替拉韦（RAL）浓度，并将其与匹配的血浆浓度和体外抑制浓度进行比较。根据包含 RAL 的治疗方案的使用情况以及 CSF 和匹配血浆样本的可用性，招募了 18 名感染 HIV-1 的受试者。通过液相色谱-串联质谱法测量 21 对 CSF 和血浆样本中的 RAL，并用逆转录-PCR（RT-PCR）检测 HIV RNA。将 RAL 浓度与野生型 HIV-1 的 50%抑制浓度（IC（50））（3.2ng/ml）进行比较。志愿者主要是感染 HIV-1 的中老年白人男性，没有丙型肝炎病毒（HCV）合并感染。中位并发 CD4（+）细胞计数为 276/μl，28%的 CD4（+）细胞计数低于 200/μl。38%的血浆标本和 4%的 CSF 标本中可检测到 HIV RNA。所有 CSF 标本中均存在 RAL，总浓度中位数为 14.5ng/ml。血浆中位数浓度为 260.9ng/ml，CSF 与血浆的中位数比值为 0.058。CSF 中的浓度与血浆中的浓度相关（r（2），0.24；P，0.02），但与给药后采样时间无关（P，>0.50）。在所有标本中，CSF 中的 RAL 浓度比野生型 HIV 的 IC（50）中位数高出 4.5 倍。RAL 存在于 CSF 中，浓度足够高，可抑制所有个体的野生型 HIV。作为有效抗逆转录病毒方案的组成部分或作为主要抗逆转录病毒药物，RAL 可能有助于控制 HIV 在神经系统中的复制。
