Abiu Sempere, Rodrigo Alonso, Leire Berrocal, Julia Calvo, Alberto Foncillas, Iván Chivite, Lorena de la Mora, Alexy Inciarte, Berta Torres, María Martínez-Rebollar, Montserrat Laguno, Ana González-Cordón, José Luis Blanco, Esteban Martínez, José M Miró, Elisa de Lazzari, Josep Mallolas, Juan Ambrosioni
{"title":"蛋白酶抑制剂在艾滋病治疗中的作用:2025年谁还需要它们?","authors":"Abiu Sempere, Rodrigo Alonso, Leire Berrocal, Julia Calvo, Alberto Foncillas, Iván Chivite, Lorena de la Mora, Alexy Inciarte, Berta Torres, María Martínez-Rebollar, Montserrat Laguno, Ana González-Cordón, José Luis Blanco, Esteban Martínez, José M Miró, Elisa de Lazzari, Josep Mallolas, Juan Ambrosioni","doi":"10.1007/s40121-025-01229-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong> Protease inhibitors (PIs) remain an effective antiretroviral therapy (ART) option for people with human immunodeficiency virus (HIV) (PWH), particularly in complex clinical and virological scenarios. However, they are associated with greater metabolic toxicity and drug-drug interactions (DDI) compared with newer ART classes. This study aimed to characterize PWH currently receiving PI-based ART and to explore the reasons for maintaining these regimens.</p><p><strong>Methods: </strong> We conducted a cross-sectional, observational study of all PWH on PI-based ART as of 30 June 2024 at the HIV Unit of Hospital Clínic de Barcelona. Demographic, clinical, laboratory, ART history, and genotypic resistance data were extracted from the institutional database and compared with the rest of the cohort.</p><p><strong>Results: </strong> Among 6261 PWH on ART, 724 (11.6%) were receiving a regimen including a PI; their use progressively declined over the last two decades (p < 0.001). The most frequent reasons for PI prescription were prior virological failure (36%) and toxicity to previous ART (41%). Compared with other PWH, those on PIs were older (median 54 versus 48 years, p < 0.001), more frequently female patients (19% versus 13%, p < 0.001), and had higher rates of heterosexual (33% versus 21%, p < 0.001) and injection-drug-use transmission (15% versus 7%, p < 0.001). Virological suppression was significantly lower among PWH on PIs (88% versus 96%, p < 0.001). Genotypic resistance testing prior to PI prescription was available for 435 PWH; 74% had at least one major resistance substitution, and 70.4% had substitutions affecting two or more antiretroviral classes. In total, 299 PWH had experienced either virological failure or toxicity to non-nucleoside reverse transcriptase inhibitor (NNRTI)- or integrase strand transfer inhibitor (InSTI)-based regimens prior to initiating a PI-based regimen. Among them, 42 had documented failure of or toxicity to both drug classes.</p><p><strong>Conclusions: </strong> Although their use has declined, a substantial number of PWH remain on regimens including a PI. These PWH typically have long-standing infections, prior ART failures, and documented resistance substitutions, supporting the continued use of PIs when other therapeutic options are limited.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Role of Protease Inhibitors in HIV Treatment: Who Still Needs Them in 2025?\",\"authors\":\"Abiu Sempere, Rodrigo Alonso, Leire Berrocal, Julia Calvo, Alberto Foncillas, Iván Chivite, Lorena de la Mora, Alexy Inciarte, Berta Torres, María Martínez-Rebollar, Montserrat Laguno, Ana González-Cordón, José Luis Blanco, Esteban Martínez, José M Miró, Elisa de Lazzari, Josep Mallolas, Juan Ambrosioni\",\"doi\":\"10.1007/s40121-025-01229-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong> Protease inhibitors (PIs) remain an effective antiretroviral therapy (ART) option for people with human immunodeficiency virus (HIV) (PWH), particularly in complex clinical and virological scenarios. However, they are associated with greater metabolic toxicity and drug-drug interactions (DDI) compared with newer ART classes. This study aimed to characterize PWH currently receiving PI-based ART and to explore the reasons for maintaining these regimens.</p><p><strong>Methods: </strong> We conducted a cross-sectional, observational study of all PWH on PI-based ART as of 30 June 2024 at the HIV Unit of Hospital Clínic de Barcelona. Demographic, clinical, laboratory, ART history, and genotypic resistance data were extracted from the institutional database and compared with the rest of the cohort.</p><p><strong>Results: </strong> Among 6261 PWH on ART, 724 (11.6%) were receiving a regimen including a PI; their use progressively declined over the last two decades (p < 0.001). The most frequent reasons for PI prescription were prior virological failure (36%) and toxicity to previous ART (41%). Compared with other PWH, those on PIs were older (median 54 versus 48 years, p < 0.001), more frequently female patients (19% versus 13%, p < 0.001), and had higher rates of heterosexual (33% versus 21%, p < 0.001) and injection-drug-use transmission (15% versus 7%, p < 0.001). Virological suppression was significantly lower among PWH on PIs (88% versus 96%, p < 0.001). Genotypic resistance testing prior to PI prescription was available for 435 PWH; 74% had at least one major resistance substitution, and 70.4% had substitutions affecting two or more antiretroviral classes. In total, 299 PWH had experienced either virological failure or toxicity to non-nucleoside reverse transcriptase inhibitor (NNRTI)- or integrase strand transfer inhibitor (InSTI)-based regimens prior to initiating a PI-based regimen. Among them, 42 had documented failure of or toxicity to both drug classes.</p><p><strong>Conclusions: </strong> Although their use has declined, a substantial number of PWH remain on regimens including a PI. These PWH typically have long-standing infections, prior ART failures, and documented resistance substitutions, supporting the continued use of PIs when other therapeutic options are limited.</p>\",\"PeriodicalId\":13592,\"journal\":{\"name\":\"Infectious Diseases and Therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2025-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Infectious Diseases and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40121-025-01229-9\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Infectious Diseases and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40121-025-01229-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
摘要
蛋白酶抑制剂(pi)仍然是人类免疫缺陷病毒(HIV) (PWH)患者有效的抗逆转录病毒治疗(ART)选择,特别是在复杂的临床和病毒学情况下。然而,与较新的抗逆转录病毒药物相比,它们具有更大的代谢毒性和药物-药物相互作用(DDI)。本研究旨在描述目前接受基于pi的ART治疗的PWH的特征,并探讨维持这些治疗方案的原因。方法:我们对截至2024年6月30日在Clínic de Barcelona医院HIV部门接受基于pi的ART治疗的所有PWH进行了一项横断面观察研究。从机构数据库中提取人口统计学、临床、实验室、ART史和基因型耐药数据,并与其他队列进行比较。结果:6261例接受ART治疗的PWH中,724例(11.6%)接受了包含PI的方案;在过去的二十年中,它们的使用逐渐下降(p结论:尽管它们的使用有所下降,但相当数量的PWH仍然使用包括PI在内的方案。这些PWH患者通常长期感染,既往ART治疗失败,并有耐药替代记录,在其他治疗选择有限的情况下支持继续使用pi。
The Role of Protease Inhibitors in HIV Treatment: Who Still Needs Them in 2025?
Introduction: Protease inhibitors (PIs) remain an effective antiretroviral therapy (ART) option for people with human immunodeficiency virus (HIV) (PWH), particularly in complex clinical and virological scenarios. However, they are associated with greater metabolic toxicity and drug-drug interactions (DDI) compared with newer ART classes. This study aimed to characterize PWH currently receiving PI-based ART and to explore the reasons for maintaining these regimens.
Methods: We conducted a cross-sectional, observational study of all PWH on PI-based ART as of 30 June 2024 at the HIV Unit of Hospital Clínic de Barcelona. Demographic, clinical, laboratory, ART history, and genotypic resistance data were extracted from the institutional database and compared with the rest of the cohort.
Results: Among 6261 PWH on ART, 724 (11.6%) were receiving a regimen including a PI; their use progressively declined over the last two decades (p < 0.001). The most frequent reasons for PI prescription were prior virological failure (36%) and toxicity to previous ART (41%). Compared with other PWH, those on PIs were older (median 54 versus 48 years, p < 0.001), more frequently female patients (19% versus 13%, p < 0.001), and had higher rates of heterosexual (33% versus 21%, p < 0.001) and injection-drug-use transmission (15% versus 7%, p < 0.001). Virological suppression was significantly lower among PWH on PIs (88% versus 96%, p < 0.001). Genotypic resistance testing prior to PI prescription was available for 435 PWH; 74% had at least one major resistance substitution, and 70.4% had substitutions affecting two or more antiretroviral classes. In total, 299 PWH had experienced either virological failure or toxicity to non-nucleoside reverse transcriptase inhibitor (NNRTI)- or integrase strand transfer inhibitor (InSTI)-based regimens prior to initiating a PI-based regimen. Among them, 42 had documented failure of or toxicity to both drug classes.
Conclusions: Although their use has declined, a substantial number of PWH remain on regimens including a PI. These PWH typically have long-standing infections, prior ART failures, and documented resistance substitutions, supporting the continued use of PIs when other therapeutic options are limited.
期刊介绍:
Infectious Diseases and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of infectious disease therapies and interventions, including vaccines and devices. Studies relating to diagnostic products and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
Areas of focus include, but are not limited to, bacterial and fungal infections, viral infections (including HIV/AIDS and hepatitis), parasitological diseases, tuberculosis and other mycobacterial diseases, vaccinations and other interventions, and drug-resistance, chronic infections, epidemiology and tropical, emergent, pediatric, dermal and sexually-transmitted diseases.