背景:体外传代实验对于开发抗逆转录病毒(ARV)药物至关重要。
方法:我们创建了一个在线数据库,其中包含102项已发表研究的数据,其中HIV-1或HIV-2与越来越浓度的FDA批准的核苷RT抑制剂(NRTIs)一起培养,非核苷RT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)来那卡巴韦,和核苷RT易位抑制剂(NRTTI)islatravir。我们总结了在NRTIs拉米夫定(3TC)传代实验的子集中选择的突变,恩曲他滨(FTC),阿巴卡韦(ABC),替诺福韦(TFV),和齐多夫定(AZT),NNRTIsdoravirine(DOR),efavirenz(EFV),和利匹韦林(RPV),INSTIsbictegravir(BIC),cabotegravir(CAB),和dolutegravir(DTG),和PI阿扎那韦(ATV),darunavir(DRV),和洛匹那韦(LPV)。将体外选择的突变与接受相同ARV的人中选择的突变进行比较。
结果:27项研究描述了用3TC传代的89个野生型分离株的实验,联邦贸易委员会,ABC,TFV,或AZT;16项研究描述了用EFV传代的89个实验,RPV,或DOR;11项研究描述了与INSTIsBIC传代的76个实验,CAB,或DTG;六项研究描述了33个与ATV传代的实验,LPV,或DRV。除了几个例外,在两个或两个以上实验中选择的突变是在接受相同ARV的患者中选择的最常见突变之一.
结论:我们创建了已发表的ARV体外选择实验的数据库。从这些实验中出现的突变通常预测在接受相同ARV的人中观察到的突变。然而,体外和体内设置之间的突变频率存在显着差异。
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.