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分析 HIV 准种和 HIV D+/R+肝肾联合移植的病毒学结果。

Analysis of HIV quasispecies and virological outcome of an HIV D+/R+ kidney-liver transplantation.

机构信息

Virology Unit, National Institute for Infectious Diseases, I.R.C.C.S. L.Spallanzani, Via Portuense, 292, 00149, Rome, Italy.

Hepatology Unit, P.O.I.T. San Camillo-Spallanzani, Rome, Italy.

出版信息

Virol J. 2022 Jan 6;19(1):4. doi: 10.1186/s12985-021-01730-w.

Abstract

INTRODUCTION

Transplantation among HIV positive patients may be a valuable therapeutic intervention. This study involves an HIV D+/R+ kidney-liver transplantation, where PBMC-associated HIV quasispecies were analyzed in donor and transplant recipients (TR) prior to transplantation and thereafter, together with standard viral monitoring.

METHODS

The donor was a 54 year of age HIV infected woman: kidney and liver recipients were two HIV infected men, aged 49 and 61. HIV quasispecies in PBMC was analyzed by ultra-deep sequencing of V3 env region. During TR follow-up, plasma HIV-1 RNA, HIV-1 DNA in PBMC, analysis of proviral integration sites and drug-resistance genotyping were performed. Other virological and immunological monitoring included CMV and EBV DNA quantification in blood and CD4 T cell counts.

RESULTS

Donor and TR were all ART-HIV suppressed at transplantation. Thereafter, TR maintained a nearly suppressed HIV-1 viremia, but HIV-1 RNA blips and the increase of proviral integration sites in PBMC attested some residual HIV replication. A transient peak in HIV-1 DNA occurred in the liver recipient. No major changes of drug-resistance genotype were detected after transplantation. CMV and EBV transient reactivations were observed only in the kidney recipient, but did not require specific treatment. CD4 counts remained stable. No intermixed quasispecies between donor and TR was observed at transplantation or thereafter. Despite signs of viral evolution in TR, HIV genetic heterogeneity did not increase over the course of the months of follow up.

CONCLUSIONS

No evidence of HIV superinfection was observed in the donor nor in the recipients. The immunosuppressive treatment administrated to TR did not result in clinical relevant viral reactivations.

摘要

介绍

在 HIV 阳性患者中进行移植可能是一种有价值的治疗干预措施。本研究涉及一名 HIV D+/R+ 的肾肝联合移植患者,在移植前和移植后对供体和移植受者(TR)的 PBMC 相关 HIV 准种进行了分析,同时进行了标准的病毒监测。

方法

供体是一名 54 岁的 HIV 感染者:两名 HIV 感染者为肾和肝接受者,年龄分别为 49 岁和 61 岁。通过对 V3 env 区进行超深度测序分析 PBMC 中的 HIV 准种。在 TR 随访期间,进行了血浆 HIV-1 RNA、PBMC 中的 HIV-1 DNA、前病毒整合位点分析和耐药基因型检测。其他病毒学和免疫学监测包括血液中 CMV 和 EBV DNA 定量和 CD4 T 细胞计数。

结果

供体和 TR 在移植时均接受 ART 治疗抑制了 HIV。此后,TR 维持了近乎抑制的 HIV-1 病毒血症,但 HIV-1 RNA 峰值和 PBMC 中前病毒整合位点的增加表明存在一些残留的 HIV 复制。肝接受者的 HIV-1 DNA 短暂出现峰值。移植后未检测到耐药基因型的主要变化。仅在肾接受者中观察到 CMV 和 EBV 的短暂再激活,但无需特殊治疗。CD4 计数保持稳定。在移植时或之后,未观察到供体和 TR 之间存在混合准种。尽管 TR 中存在病毒进化的迹象,但在随访的几个月中,HIV 遗传异质性并未增加。

结论

在供体和受者中均未观察到 HIV 超感染的证据。TR 接受的免疫抑制治疗并未导致临床相关的病毒再激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c479/8739652/c3dd36eddd08/12985_2021_1730_Fig1_HTML.jpg

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