Research progress on second-generation integrase strand transfer inhibitor-based fixed-dose combination therapies
Defu Yuan1
Fei Zhao2
Shanshan Liu1
Hongxia Yan2
Lifeng Liu2
Tong Zhang2
Bei Wang1
Bin Su3
1.Department of Epidemiology and Health Statistics,School of Public Health,Southeast University,Nanjing 210009,Jiangsu,China2.Beijing Key Laboratory for HIV/AIDS Research,Sino-French Joint Laboratory for HIV/AIDS Research,Clinical and Research Center for Infectious Diseases,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China3.Beijing Key Laboratory for HIV/AIDS Research,Sino-French Joint Laboratory for HIV/AIDS Research,Clinical and Research Center for Infectious Diseases,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China;Central Laboratory,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China;The Scientific and Technological Achievement Transformation Center,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China
摘要：Integrase Strand Transfer Inhibitors(INSTIs)have favorable safety and tolerability profiles,potent antiviral activ-ity,and high resistance barriers,solving the limitations of previous antiretrovirals caused by resistant mutations.While first-generation INSTIs have exhibited emerging resistance challenges during extended clinical use,sec-ond-generation INSTIs provide enhanced resistance barriers and extended plasma half-lives relative to their prede-cessors.Optimized combination regimens incorporating these agents have substantially improved therapeutic con-venience and long-term disease management in human immunodeficiency virus(HIV)care.Current investigations focus on multiple combination strategies employing second-generation INSTIs including dolutegravir(DTG)and bictegravir(BIC),with preliminary findings demonstrating substantial clinical benefits.The DTG/lamivudine(3TC)dual regimen in the GEMINI and TANGO studies achieved 92.1%-99.6%virologic suppression rates at week 48,maintaining efficacy through 144 weeks.The cabotegravir(CAB)/Rilpivirine(RPV)long-acting injectable combi-nation in ATLAS trials demonstrated 92.5%suppression efficacy with validated every-two-month dosing intervals.The BIC/emtricitabine/tenofovir alafenamide triple regimen in studies 1489/1490 maintained>84%suppression at week 144 while retaining activity against resistant variants.Real-world data confirm that these regimens main-tained a viral suppression rate of>90%in both treatment-naïve and-experienced patients,with treatment inter-ruption rates of<5%.Recent advances include the US Food and Drug Administration's approval of DTG/3TC for use in adolescents≥12 years old and adaptive studies of CAB/RPV in special populations.This article summariz-es the research progress of current combination formulations based on second-generation INSTIs to provide new therapeutic options and clinical insights for the treatment of patients with HIV.
机标关键词：generationresearchsecondcombinationfixed-doseinhibitor-basedintegraseprogress
论文发表日期：2025-06-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：15( 2-16 )
英文信息