De Bellis Emanuela, Donnarumma Danilo, Zarrella Adele, Mazzeo Salvatore Maria, Pagano Annarita, Manzo Valentina, Mazza Ines, Sabbatino Francesco, Corbi Graziamaria, Pagliano Pasquale, Filippelli Amelia, Conti Valeria
School "Clinical and Translational Oncology (CTO)", Scuola Superiore Meridionale, University of Naples "Federico II", 80138 Naples, Italy.
Postgraduate School of Clinical Pharmacology and Toxicology, University of Salerno, 84081 Baronissi, Italy.
Pharmaceutics. 2024 Dec 28;17(1):31. doi: 10.3390/pharmaceutics17010031.
Highly active antiretroviral therapy has led to a significant increase in the life expectancy of people living with HIV. The trade-off is that HIV-infected patients often suffer from comorbidities that require additional treatment, increasing the risk of Drug-Drug Interactions (DDIs), the clinical relevance of which has often not been determined during registration trials of the drugs involved. Therefore, it is important to identify potential clinically relevant DDIs in order to establish the most appropriate therapeutic approaches. This review aims to summarize and analyze data from studies published over the last two decades on DDI-related adverse clinical outcomes involving anti-HIV drugs and those used to treat comorbidities. Several studies have examined the pharmacokinetics and tolerability of different drug combinations. Protease inhibitors, followed by nonnucleoside reverse transcriptase inhibitors and integrase inhibitors have been recognized as the main players in DDIs with antivirals used to control co-infection, such as Hepatitis C virus, or with drugs commonly used to treat HIV comorbidities, such as lipid-lowering agents, proton pump inhibitors and anticancer drugs. However, the studies do not seem to be consistent with regard to sample size and follow-up, the drugs involved, or the results obtained. It should be noted that most of the available studies were conducted in healthy volunteers without being replicated in patients. This hampered the assessment of the clinical burden of DDIs and, consequently, the optimal pharmacological management of people living with HIV.
高效抗逆转录病毒疗法显著提高了艾滋病毒感染者的预期寿命。然而，权衡之处在于，艾滋病毒感染患者常常患有需要额外治疗的合并症，这增加了药物相互作用（DDIs）的风险，而在相关药物的注册试验中，其临床相关性往往尚未得到确定。因此，识别潜在的具有临床相关性的药物相互作用，对于确立最恰当的治疗方法至关重要。本综述旨在总结和分析过去二十年来发表的有关涉及抗艾滋病毒药物和用于治疗合并症药物的药物相互作用相关不良临床结局的研究数据。多项研究已考察了不同药物组合的药代动力学和耐受性。蛋白酶抑制剂，其次是非核苷类逆转录酶抑制剂和整合酶抑制剂，已被确认为与用于控制合并感染（如丙型肝炎病毒）的抗病毒药物，或与常用于治疗艾滋病毒合并症的药物（如降脂药、质子泵抑制剂和抗癌药）发生药物相互作用的主要因素。然而，这些研究在样本量和随访、所涉及的药物或所获得的结果方面似乎并不一致。应当指出的是，现有的大多数研究是在健康志愿者中进行的，并未在患者中重复验证。这妨碍了对药物相互作用临床负担的评估，进而妨碍了对艾滋病毒感染者的最佳药物管理。
