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Genomic instability in people living with HIV
Mutation Research/Genetic Toxicology and Environmental Mutagenesis ( IF 2.3 ) Pub Date : 2021-02-18 , DOI: 10.1016/j.mrgentox.2021.503336
Juan Ernesto Gutiérrez-Sevilla 1 , Jhonathan Cárdenas-Bedoya 2 , Martha Escoto-Delgadillo 3 , Guillermo Moisés Zúñiga-González 4 , Alma Minerva Pérez-Ríos 5 , Belinda Claudia Gómez-Meda 6 , Gracia Viviana González-Enríquez 7 , Izchel Figarola-Centurión 8 , Efraín Chavarría-Avila 7 , Blanca Miriam Torres-Mendoza 2
Affiliation  

The increased life expectancy of people living with HIV (PLWH) receiving antiretroviral treatment (ART) has transformed HIV infection into a chronic disease. However, patients may be at risk of accelerated aging and the accumulation of cellular damage, which may trigger the development of cancer. We evaluated genomic instability in HIV-positive individuals with different viral loads receiving antiretroviral treatment (ART) and in HIV ART-naïve individuals. We included 67 participants divided into four groups: group 1 (n = 24) HIV patients receiving reverse-transcriptase inhibitors (tenofovir/ emtricitabine/ efavirenz and abacavir/ lamivudine/ efavirenz), group 2 (n = 22) HIV patients receiving protease inhibitors combined with other antiretroviral drugs (tenofovir/ emtricitabine with ritonavir/ atazanavir or lopinavir/ ritonavir, and darunavir/ ritonavir/ raltegravir), group 3 (n = 13) HIV ART-naïve patients, and group 4 (n = 8) healthy individuals (controls). Nuclear abnormalities in buccal mucosal samples (micronuclei, binucleated cells, nuclear buds, karyorrhexis, karyolysis, and pyknosis) were quantified. Simultaneously, blood samples were taken to quantify CD4+, CD8+, and HIV viral load. There was a significant age difference between HIV ART-naïve patients and receiving ART groups. Infection time was longer in HIV patients with ART than in ART-naïve patients. There were no differences in sex, smoking, alcohol consumption, or number of micronucleated cells between the study groups. We found higher frequencies of binucleated cells and nuclear buds in HIV patients, HIV ART-naïve, and HIV ART patients compared to the control group. We found a positive correlation between nuclear buds and CD4/CD8 ratio in the HIV ART-naïve group. In conclusion, PLWH showed increased genomic instability. The CD4/CD8 ratio affects the numbers of nuclear buds and binucleated cells. These findings are pertinent to mechanisms of damage and possible strategies to mitigate carcinogenesis in PLWH.



中文翻译:

HIV感染者的基因组不稳定

接受抗逆转录病毒治疗 (ART) 的 HIV 感染者 (PLWH) 的预期寿命延长,已将 HIV 感染转变为慢性疾病。然而,患者可能面临加速衰老和细胞损伤积累的风险,这可能会引发癌症的发展。我们评估了接受抗逆转录病毒治疗 (ART) 的具有不同病毒载量的 HIV 阳性个体和未接受 HIV ART 个体的基因组不稳定性。我们将 67 名参与者分为四组:第 1 组(n = 24)接受逆转录酶抑制剂(替诺福韦/恩曲他滨/依法韦仑和阿巴卡韦/拉米夫定/依法韦仑)的 HIV 患者,第 2 组(n = 22)接受蛋白酶抑制剂联合治疗的 HIV 患者与其他抗逆转录病毒药物(替诺福韦/恩曲他滨联合利托那韦/阿扎那韦或洛匹那韦/利托那韦,和 darunavir/ritonavir/raltegravir)、第 3 组(n = 13)HIV ART 初治患者和第 4 组(n = 8)健康个体(对照组)。对口腔粘膜样品(微核、双核细胞、核芽、核破裂、核溶解和固缩)中的核异常进行了量化。同时,采集血液样本以量化 CD4+、CD8+ 和 HIV 病毒载量。未接受过 HIV ART 患者和接受 ART 组之间存在显着的年龄差异。接受 ART 的 HIV 患者的感染时间比未接受 ART 的患者长。研究组之间在性别、吸烟、饮酒或微核细胞数量方面没有差异。我们发现与对照组相比,HIV 患者、HIV ART 初治患者和 HIV ART 患者中双核细胞和核芽的频率更高。我们发现未接受 HIV ART 组的核芽与 CD4/CD8 比率呈正相关。总之,PLWH 显示出基因组不稳定性增加。CD4/CD8 比率影响核芽和双核细胞的数量。这些发现与损伤机制和减轻 PLWH 致癌作用的可能策略有关。

更新日期:2021-02-23
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