University of Washington and Seattle Children's Research Institute, Seattle, WA, USA.
Harvard T.H. Chan School of Public Health, Boston, MA, USA.
AIDS. 2024 Aug 1;38(10):1494-1504. doi: 10.1097/QAD.0000000000003937. Epub 2024 Jun 4.
Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF).
IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study.
Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) more than 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIV pol/gag -DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair.
Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. Nine of 18 (50%) were female sex-at-birth, and 14 of 18 (78%) were black. Median (range) age was 20 years (13-27), time on ART was 18.3 years (8.0-25.5), and FCCS was 68 (53-80). HIV-DNA was detected in PBMCs from all participants. In CSF, two of 18 (11%, 95% CI: 1.4-34.7%) participants had detectable cell-free HIV-RNA, while HIV gag or pol -DNA was detectable in 13 of 18 (72%, 95% confidence interval: 47-90). Detectable HIV-DNA in CSF was associated with male sex-at-birth ( P = 0.051), lower CD4 + cell count at enrollment ( P = 0.016), and higher PBMC HIV pol -DNA copies ( P = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection.
We found that a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.
中枢神经系统（CNS）HIV 感染会影响认知能力，可能会成为围生期 HIV（AYAPHIV）青少年和年轻成人治愈的障碍。IMPACT2015 招募了接受抑制性抗逆转录病毒治疗（ART）且有认知障碍的 AYAPHIV，以检测和量化血液和脑脊液（CSF）中的 HIV。
IMPACT2015 是一项基于美国的多地点、探索性、观察性研究。
认知障碍定义为 NIH 工具包液体认知综合评分（FCCS）低于年龄调整正常组平均值一个标准差以上。对配对 CSF 和血液中的无细胞 HIV-RNA 和细胞相关 HIV pol/gag-DNA 以及 10 种炎症/神经元损伤生物标志物进行了测量。头发中量化了 ART 暴露浓度。
在 24 名参与者中，有 20 名成功采集了 CSF，有 18 名也符合病毒抑制标准。18 名中的 9 名（50%）为出生时的女性，18 名中的 14 名（78%）为黑人。中位（范围）年龄为 20 岁（13-27 岁），ART 时间为 18.3 年（8.0-25.5 年），FCCS 为 68（53-80）。所有参与者的 PBMC 中均检测到 HIV-DNA。在 CSF 中，18 名参与者中有 2 名（11%，95%CI：1.4-34.7%）可检测到无细胞 HIV-RNA，而 18 名中有 13 名（72%，95%置信区间：47-90%）可检测到 HIV gag 或 pol-DNA。CSF 中可检测到 HIV-DNA 与出生时的男性（P=0.051）、入组时的 CD4+细胞计数较低（P=0.016）和 PBMC HIV pol-DNA 拷贝数较高（P=0.058）有关。头发抗逆转录病毒浓度和生物标志物与 CSF HIV-DNA 检测无关。
我们发现，在长期病毒抑制期间，大量有神经认知障碍的 AYAPHIV 有 CSF 细胞携带 HIV-DNA。CSF 中持续存在 HIV-DNA 的这一证据表明，中枢神经系统应在治疗和治愈研究中被考虑。
