Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139,7), Bobadela LRS 2695-066, Portugal.
CNC - Center for Neuroscience and Cell Biology; Rua Larga, FMUC, Polo I, 1ºandar, Universidade de Coimbra, Coimbra 3004-517, Portugal.
Curr Med Chem. 2020;27(5):760-794. doi: 10.2174/0929867325666180904123549.
Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To- Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process. These classes encompass Non- Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged and maximal viral suppression, and preservation of the immune system upon HIV infection. Still, the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, the development of drug resistance, and the lack of patient compliance compromise the complete HIV elimination. The development of nanotechnology-based drug delivery systems may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics and pharmacokinetic properties.
儿童获得性免疫缺陷综合征（AIDS）是一种危及生命的传染病，人类免疫缺陷病毒（HIV）主要通过母婴传播（MTCT）在妊娠、分娩和哺乳期间传播。本综述概述了消除儿童 HIV-1 感染中全身病毒复制的独特治疗选择。许多类抗逆转录病毒药物已成为下调 HIV 复制过程中不同步骤的治疗工具。这些类别包括非核苷类逆转录酶抑制剂（NNRTIs）、核苷/核苷酸类逆转录酶抑制剂（NRTIs/NtRTIs）、整合酶抑制剂（INIs）、蛋白酶抑制剂（PIs）和进入抑制剂（EIs）。某些抗逆转录病毒药物与药代动力学增强剂（PEs）联合使用可能会提高主要治疗药物的疗效。多种抗逆转录病毒药物联合治疗方案（高效抗逆转录病毒治疗 - HAART）是目前 HIV 感染的标准治疗方法。到目前为止，HAART 的使用为延长和最大限度地抑制病毒提供了最佳机会，并在 HIV 感染时保留了免疫系统。然而，频繁给予高剂量的多种药物、其无法以足够剂量到达病毒储存库的低效能力、耐药性的发展以及缺乏患者依从性，都影响了 HIV 的完全消除。基于纳米技术的药物传递系统的发展可能使抗逆转录病毒药物能够以治疗浓度靶向递送至无法到达的病毒储存库部位。此外，计算机辅助药物设计（CADD）方法的应用为开发具有良好药效学和药代动力学特性的抗 HIV 药物候选物提供了有价值的工具。
