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抗逆转录病毒体外传代实验中选择的 HIV 突变综合数据库。

Comprehensive database of HIV mutations selected during antiretroviral in vitro passage experiments.

机构信息

Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, 94305, USA.

Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, 94305, USA.

出版信息

Antiviral Res. 2024 Oct;230:105988. doi: 10.1016/j.antiviral.2024.105988. Epub 2024 Aug 16.

Abstract

BACKGROUND

In vitro passage experiments are crucial to the development of antiretroviral (ARV) drugs.

METHODS

We created an online database containing data from 102 published studies in which HIV-1 or HIV-2 was cultured with increasing concentrations of the FDA-approved nucleoside RT inhibitors (NRTIs), nonnucleoside RT inhibitors (NNRTIs), integrase strand transfer inhibitors (INSTIs), protease inhibitors (PIs), capsid inhibitor (CAI) lenacapavir, and nucleoside RT translocation inhibitor (NRTTI) islatravir. We summarized the mutations selected in the subset of passage experiments with NRTIs lamivudine (3TC), emtricitabine (FTC), abacavir (ABC), tenofovir (TFV), and zidovudine (AZT), NNRTIs doravirine (DOR), efavirenz (EFV), and rilpivirine (RPV), INSTIs bictegravir (BIC), cabotegravir (CAB), and dolutegravir (DTG), and PIs atazanavir (ATV), darunavir (DRV), and lopinavir (LPV). Mutations selected in vitro were compared with those selected in persons receiving the same ARV.

RESULTS

Twenty-seven studies described 89 experiments of wildtype isolates passaged with 3TC, FTC, ABC, TFV, or AZT; sixteen studies described 89 experiments passaged with EFV, RPV, or DOR; eleven studies described 76 experiments passaged with the INSTIs BIC, CAB, or DTG; six studies described 33 experiments passaged with ATV, LPV, or DRV. With several exceptions, mutations selected in two or more experiments were among the most common mutations selected in persons receiving the same ARV.

CONCLUSIONS

We created a database of published ARV in vitro selection experiments. Mutations emerging from these experiments generally predict those observed in persons receiving the same ARV. However, there are notable differences in mutation frequencies between in vitro and in vivo settings.

摘要

背景

体外传代实验对于抗逆转录病毒(ARV)药物的开发至关重要。

方法

我们创建了一个在线数据库,其中包含 102 篇已发表研究的的数据,这些研究中 HIV-1 或 HIV-2 与 FDA 批准的核苷逆转录酶抑制剂(NRTIs)、非核苷逆转录酶抑制剂(NNRTIs)、整合酶链转移抑制剂(INSTIs)、蛋白酶抑制剂(PIs)、衣壳抑制剂(CAI)lenacapavir 和核苷逆转录酶易位抑制剂(NRTTI)islatravir 进行了浓度递增培养。我们总结了 NRTIs 拉米夫定(3TC)、恩曲他滨(FTC)、阿巴卡韦(ABC)、替诺福韦(TFV)和齐多夫定(AZT)、NNRTIs 多拉韦林(DOR)、依非韦伦(EFV)和利匹韦林(RPV)、INSTIs 比克替拉韦(BIC)、卡博特韦(CAB)和度鲁特韦(DTG)和 PIs 阿扎那韦(ATV)、达芦那韦(DRV)和洛匹那韦(LPV)传代实验中选择的突变与接受相同 ARV 的人群中选择的突变进行了比较。

结果

27 项研究描述了 89 项用 3TC、FTC、ABC、TFV 或 AZT 传代的野生型分离物实验;16 项研究描述了 89 项用 EFV、RPV 或 DOR 传代的实验;11 项研究描述了 76 项用 INSTIs BIC、CAB 或 DTG 传代的实验;6 项研究描述了 33 项用 ATV、LPV 或 DRV 传代的实验。除了一些例外,两个或更多实验中选择的突变通常是接受相同 ARV 的人群中最常见的突变。

结论

我们创建了一个已发表的 ARV 体外选择实验数据库。这些实验中出现的突变通常可以预测接受相同 ARV 的人群中出现的突变。然而,在体外和体内环境中,突变频率存在显著差异。

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