Antiretroviral therapy (ART) can attain prolonged undetectable HIV-1 in plasma and cerebrospinal fluid (CSF), but brain injury remains prevalent in people living with HIV-1 infection (PLHIV). We investigated cell-associated (CA)-HIV-1 RNA transcripts in cells in CSF and blood, using the highly sensitive Double-R assay, together with proton Magnetic Resonance Spectroscopy ( 1 H MRS) of major brain metabolites, in sixteen PLHIV. 14/16 CSF cell samples had quantifiable CA-HIV-1 RNA, at levels significantly higher than in their PBMCs (median 9,266 vs 185 copies /106 CD4+ T-cells; p<0.0001). In individual PLHIV, higher levels of HIV-1 transcripts in CSF cells were associated with greater brain injury in the frontal white matter (Std β=-0.73; p=0.007) and posterior cingulate (Std β=-0.61; p=0.03). 18-colour flow cytometry revealed that the CSF cells were 91% memory T-cells, equally CD4+ and CD8+ T-cells, but fewer B cells (0.4 %), and monocytes (3.1%). CXCR3 + CD49d + integrin β7-, CCR5 + CD4 + T-cells were highly enriched in CSF, compared with PBMC (p <0.001). However, CA-HIV-1 RNA could not be detected in 10/16 preparations of highly purified monocytes from PBMC, and was extremely low in the other six. Our data show that elevated HIV-1 transcripts in CSF cells were associated with brain injury, despite suppressive ART. The cellular source is most likely memory CD4 + T cells from blood, rather than trafficking monocytes. Future research should focus on inhibitors of this transcription to reduce local production of potentially neurotoxic and inflammatory viral products.

中文翻译：

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尽管有效的抗逆转录病毒治疗，脑脊液 CD4+ T 细胞中细胞相关 HIV-1 转录物的升高与脑损伤有关

抗逆转录病毒疗法 (ART) 可使血浆和脑脊液 (CSF) 中的 HIV-1 长时间检测不到，但脑损伤在 HIV-1 感染者 (PLHIV) 中仍然普遍存在。我们使用高度灵敏的双 R 测定法和质子磁共振波谱法研究了 CSF 和血液中细胞中的细胞相关 (CA)-HIV-1 RNA 转录物（1个H MRS) 的主要脑代谢物，在 16 个 PLHIV 中。14/16 CSF 细胞样本具有可量化的 CA-HIV-1 RNA，其水平显着高于其 PBMC（中位数 9,266 vs 185 拷贝/106 CD4+ T 细胞；p<0.0001）。在个体 PLHIV 中，CSF 细胞中较高水平的 HIV-1 转录物与额叶白质（Std β=-0.73；p=0.007）和后扣带回（Std β=-0.61；p=0.03）的脑损伤程度更高有关. 18 色流式细胞仪显示 CSF 细胞中 91% 是记忆 T 细胞，同样是 CD4+ 和 CD8+ T 细胞，但 B 细胞 (0.4%) 和单核细胞 (3.1%) 较少。CXCR3+CD49d+整合素 β7-, CCR5+CD4+与 PBMC 相比，T 细胞在 CSF 中高度富集 (p <0.001)。然而，在来自 PBMC 的高度纯化单核细胞的 10/16 制剂​​中无法检测到 CA-HIV-1 RNA，而在其他六种中则极低。我们的数据表明，尽管采用抑制性 ART，CSF 细胞中 HIV-1 转录物升高与脑损伤有关。细胞来源很可能是记忆CD4+来自血液的 T 细胞，而不是贩运单核细胞。未来的研究应该集中在这种转录的抑制剂上，以减少潜在神经毒性和炎症病毒产物的局部产生。