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原病毒HIV-1 DNA基因分型在接受抗逆转录病毒治疗时病毒血症水平较低的HIV感染者(PLWH)中的作用。

Role of Proviral HIV-1 DNA Genotyping for People Living with HIV (PLWH) Who Had Low-Level Viremia While Receiving Antiretroviral Therapy.

作者信息

Lv Shiyun, Sun Lijun, Li Tongzeng, Bai Ruojing, Dai Man, Wang Ran, Zhai Yuanyi, Hua Wei, Li Aixin, Xin Ruolei, Dai Lili

机构信息

Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China.

Institute for STD/AIDS Prevention and Treatment, Beijing Center for Disease Prevention and Control, Beijing, People's Republic of China.

出版信息

Infect Drug Resist. 2023 Jul 19;16:4697-4706. doi: 10.2147/IDR.S406188. eCollection 2023.

Abstract

OBJECTIVE

To analyze the antiretroviral resistance in people living with HIV (PLWH) who developed low-level viremia (LLV) during antiretroviral therapy (ART) via sequencing of their HIV-1 proviral DNA and RNA and comparisons of their proviral DNA genotyping data with their past and synchronous RNA genotyping data.

PATIENTS AND METHODS

PLWH with LLV while receiving ART for 6 months or longer from January 2020 to September 2021 were included. HIV-1 proviral DNA and RNA were extracted from white-blood cells and concentrated plasma by ultracentrifugation, respectively, and HIV-1 gene fragments were amplified and sequenced. The concordance in the detection of resistance-associated mutations (RAMs) were examined between proviral DNA vs past RNA genotyping and proviral DNA vs synchronous RNA genotyping.

RESULTS

Of the 150 PLWH with LLV, 117 proviral DNA sequences detected in 105 PLWH were successfully amplified and RAMs were present in 27.6% and the rate of RAMs conferring low-level or greater resistance to antiretrovirals examined was 17.1%. Fifty-six and 57 PLWH had results of past and synchronous RNA genotyping, respectively, for comparisons with those of proviral DNA genotyping; and the concordance rates were 76.8% and 75.4%, respectively. However, proviral DNA genotyping lost than gained partial information on antiretroviral resistance compared with past or synchronous RNA genotyping.

CONCLUSION

We found that the concordance between proviral DNA and past and synchronous RNA genotyping was moderate. Proviral DNA genotyping lost than gained more information on antiretroviral resistance compared with past or synchronous RNA genotyping. To optimize ART in PLWH with LLV, antiretroviral resistance profile should be interpreted in combination with proviral DNA and RNA genotyping and a comprehensive review of previous treatment history.

摘要

目的

通过对HIV-1前病毒DNA和RNA进行测序,并将其前病毒DNA基因分型数据与其过去和同步的RNA基因分型数据进行比较,分析在抗逆转录病毒治疗(ART)期间出现低水平病毒血症(LLV)的HIV感染者(PLWH)中的抗逆转录病毒耐药性。

患者和方法

纳入2020年1月至2021年9月期间接受ART治疗6个月或更长时间且出现LLV的PLWH。分别通过超速离心从白细胞和浓缩血浆中提取HIV-1前病毒DNA和RNA,并对HIV-1基因片段进行扩增和测序。检查前病毒DNA与过去RNA基因分型以及前病毒DNA与同步RNA基因分型之间耐药相关突变(RAMs)检测的一致性。

结果

在150例出现LLV的PLWH中,105例PLWH中检测到的117条前病毒DNA序列成功扩增,27.6%存在RAMs,对所检测的抗逆转录病毒药物产生低水平或更高耐药性的RAMs发生率为17.1%。分别有56例和57例PLWH有过去和同步RNA基因分型结果,用于与前病毒DNA基因分型结果进行比较;一致性率分别为76.8%和75.4%。然而,与过去或同步RNA基因分型相比,前病毒DNA基因分型在抗逆转录病毒耐药性方面失去的部分信息多于获得的信息。

结论

我们发现前病毒DNA与过去和同步RNA基因分型之间的一致性为中等。与过去或同步RNA基因分型相比,前病毒DNA基因分型在抗逆转录病毒耐药性方面失去的信息多于获得的信息。为了优化出现LLV的PLWH的ART,应结合前病毒DNA和RNA基因分型以及对既往治疗史的全面回顾来解释抗逆转录病毒耐药性谱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fed5/10363348/f48be508d162/IDR-16-4697-g0001.jpg

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