Department of Infectious Diseases, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
J Acquir Immune Defic Syndr. 2010 Dec 15;55(5):590-6. doi: 10.1097/QAI.0b013e3181f5b3d1.
Antiretroviral treatment (ART) significantly reduces cerebrospinal fluid (CSF) HIV-1 RNA levels and residual viremia is less frequently found in CSF than in blood. However, persistent intrathecal immunoactivation is common, even after several years of ART. To investigate whether low-level CSF viremia and residual immunoactivation within the central nervous system (CNS) derive from ongoing local viral replication, we conducted a study of treatment intensification in patients on effective ART.
Ten patients on ART with plasma HIV RNA <50 copies per milliliter for >18 months were included. Intensification was given for in total 8 weeks: 4 weeks with maraviroc or lopinavir/ritonavir (good CNS penetration), and 4 weeks with enfuvirtide (poor CNS penetration). Lumbar punctures were performed 4 weeks before, at intensification commencement, at switchover after 4 weeks, at the conclusion of, and 4 weeks after the intensification period.
No significant changes in HIV RNA, neopterin, β2-microglobulin, immunoglobulin G index, albumin ratio, and CD4(+) T-cell count were observed, either in CSF or blood, neither before, during, nor after the intensification periods.
ART intensification did not reduce residual CSF HIV RNA levels or intrathecal immunoactivation in patients on ART. These findings do not support an ongoing viral replication in CNS.
抗逆转录病毒治疗（ART）显著降低了脑脊液（CSF）中的 HIV-1 RNA 水平，并且在 CSF 中比在血液中更难发现残留的病毒血症。然而，即使在接受 ART 治疗多年后，中枢神经系统（CNS）内仍持续存在免疫激活。为了研究中枢神经系统内低水平的 CSF 病毒血症和残留免疫激活是否源自持续的局部病毒复制，我们对接受有效 ART 治疗的患者进行了治疗强化研究。
纳入了 10 名接受 ART 治疗且血浆 HIV RNA 低于 50 拷贝/毫升超过 18 个月的患者。强化治疗总共进行了 8 周：4 周使用马拉维若或洛匹那韦/利托那韦（对 CNS 有良好的穿透性），4 周使用恩夫韦肽（对 CNS 穿透性差）。在强化治疗前 4 周、强化治疗开始时、4 周转换后、结束时以及强化治疗结束后 4 周进行腰椎穿刺。
在 CSF 或血液中，无论是在强化治疗前、期间还是之后，均未观察到 HIV RNA、新蝶呤、β2-微球蛋白、免疫球蛋白 G 指数、白蛋白比值和 CD4(+) T 细胞计数有显著变化。
ART 强化治疗并未降低接受 ART 治疗的患者的 CSF 中 HIV RNA 水平或中枢神经系统内的免疫激活。这些发现不支持中枢神经系统内持续的病毒复制。
