Clinic of Infectious Diseases, University of Bari "Aldo Moro", Piazza G. Cesare, 11, 70124, Bari, Italy.
Infection. 2019 Jun;47(3):441-446. doi: 10.1007/s15010-019-01268-8. Epub 2019 Jan 16.
We aimed to evaluate HIV-1 compartmentalization between the cerebrospinal fluid (CSF) and plasma and investigate as to which extent HIV-1 strains in CSF differ from those in blood and whether a correlation with either plasma viral load (pVL) or an altered blood-brain barrier (BBB) does exist.
We retrospectively evaluated paired CSF/blood samples collected from 86 HIV+ patients. HIV-RNA quantification, pol (PR/RT), and V3 sequencing were performed. HIV coreceptor tropism (CRT) was inferred (g2p, false-positive rate 10%, FPR). Data of standard CSF analysis were also reviewed; an altered CSF/plasma albumin ratio signified BBB damage. Neurological abnormalities (NA) were recorded.
Overall, 32% of patients had a CSF/plasma HIV-RNA ratio > 1 (discordance); 3% of patients had detectable CSF HIV-RNA despite suppressed pVL (escape). Discordance was more frequent in ART-treated patients (p < 0.001) and in patients with NA (p = 0.016), but was independent of BBB damage (p = 0.65) and AIDS diagnosis (p = 0.96). Finally, CSF/plasma discordance was significantly more frequent (p < 0.0001) in patients with lower pVL values (< 10.000 copies/ml). Env divergence > 10% was found in 44% of sequences and was associated with ART (p = 0.008) and NA (p = 0.037). Overall, 24% of patients had a discordant CSF/blood CRT. A 100% nucleotide identity was observed in only 7.3% of pol sequences; notably, 10% of patients had resistance-associated mutations in CSF, but not in blood.
Our data confirm an independent replication and evolution of HIV within the CSF. A number of factors either hinder or contribute to the compartmentalization of HIV.
我们旨在评估 HIV-1 在脑脊液（CSF）和血浆之间的分隔，并研究 HIV-1 株在 CSF 中的差异程度及其与血浆病毒载量（pVL）或改变的血脑屏障（BBB）之间的相关性。
我们回顾性评估了从 86 名 HIV+患者采集的配对 CSF/血液样本。进行了 HIV-RNA 定量、pol（PR/RT）和 V3 测序。推断了 HIV 核心受体嗜性（CRT）（g2p，假阳性率 10%，FPR）。还回顾了标准 CSF 分析的数据；改变的 CSF/血浆白蛋白比值表明 BBB 损伤。记录了神经功能障碍（NA）。
总体而言，32%的患者 CSF/血浆 HIV-RNA 比值＞1（不一致）；尽管 pVL 抑制，但 3%的患者 CSF 中可检测到 HIV-RNA（逃逸）。在接受 ART 治疗的患者（p＜0.001）和有 NA 的患者（p=0.016）中，不一致更为常见，但与 BBB 损伤（p=0.65）和 AIDS 诊断（p=0.96）无关。最后，在 pVL 值较低（＜10.000 拷贝/ml）的患者中，CSF/血浆不一致更为常见（p＜0.0001）。在 44%的序列中发现 env 差异＞10%，与 ART（p=0.008）和 NA（p=0.037）相关。总体而言，24%的患者 CSF/血液 CRT 不一致。仅在 7.3%的 pol 序列中观察到 100%核苷酸同一性；值得注意的是，10%的患者 CSF 中有耐药相关突变，但血液中没有。
我们的数据证实了 HIV 在 CSF 中的独立复制和进化。许多因素阻碍或促成了 HIV 的分隔。
