The HIV attacks the immune system provoking an infection that is considered a global health challenge. Despite antiretroviral treatments being effective in reducing the plasma viral load in the blood to undetectable levels in people living with HIV (PLWH), the disease is not cured and has become chronic. This happens because of the existence of anatomical and cellular viral reservoirs, mainly located in the lymph nodes and gastrointestinal tract, which are composed of infected CD4+ T cells with a resting memory phenotype and inaccessible to antiretroviral therapy. Herein, a new therapeutic strategy based on nanotechnology is presented. Different combinations of antiretroviral drugs (bictegravir/tenofovir/emtricitabine and nevirapine/tenofovir/emtricitabine) and toll-like receptor agonists were encapsulated into metal–organic frameworks (MOFs) PCN-224 and ZIF-8. The encapsulation efficiencies of all the drugs, as well as their release rate from the carriers, were measured. In vitro studies about the cell viability, the hemocompatibility, and the platelet aggregation of the MOFs were carried out. Epifluorescence microscopy assays confirmed the ability of ZIF-8 to target a carboxyfluorescein probe inside HeLa cell lines and PBMCs. These results pave the way for the use of these structures to eliminate latent HIV reservoirs from anatomical compartments through the activation of innate immune cells, and a higher efficacy of the triplet combinations of antiretroviral drugs.

中文翻译：

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生物相容性金属有机框架作为消除艾滋病毒感染者体内艾滋病毒储存库的有前途的平台

艾滋病毒攻击免疫系统，引发感染，这被认为是全球健康挑战。尽管抗逆转录病毒治疗可以有效地将艾滋病毒感染者（PLWH）血液中的血浆病毒载量降低至不可检测的水平，但这种疾病并未治愈，而是变成了慢性病。发生这种情况是因为存在解剖学和细胞病毒库，主要位于淋巴结和胃肠道，由受感染的 CD4+ T 细胞组成，具有静息记忆表型，无法进行抗逆转录病毒治疗。在此，提出了一种基于纳米技术的新治疗策略。抗逆转录病毒药物（比克替拉韦/替诺福韦/恩曲他滨和奈韦拉平/替诺福韦/恩曲他滨）和Toll样受体激动剂的不同组合被封装到金属有机框架（MOF）PCN-224和ZIF-8中。测量了所有药物的封装效率以及它们从载体中的释放速率。对 MOF 的细胞活力、血液相容性和血小板聚集进行了体外研究。落射荧光显微镜测定证实了 ZIF-8 能够靶向 HeLa 细胞系和 PBMC 内的羧基荧光素探针。这些结果为使用这些结构通过激活先天免疫细胞从解剖区室中消除潜在的 HIV 储存库以及抗逆转录病毒药物三联体组合的更高功效铺平了道路。