Extended follow-up of randomized participants in the INSIGHT START trial

对 INSIGHT START 试验中随机参与者的长期随访

• 批准号: 10394294
• 负责人: Birgit Grund
• 金额: $ 204.35万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-17 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10394294
• 关键词: Acquired Immunodeficiency Syndrome; Address; Applications Grants; Authorization documentation; Award; Bacterial Infections; CD4 Lymphocyte Count; Calendar; Cardiovascular Diseases; Cells; Characteristics; Cirrhosis; Clinical; Clinical Trials Data Monitoring Committees; Collection; Consent; Data; Data Analyses; Data Collection; End stage renal failure; Event; Foundations; Funding; Future; Geography; Grant; HIV; HIV Seropositivity; International; International AIDS; International Network for Strategic Initiatives in Global HIV Trials; Journals; Longterm Follow-up; Malignant Neoplasms; Medicine; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; New England; Outcome; Paper; Participant; Persons; Protocols documentation; Publishing; RNA; Randomized; Recommendation; Research Personnel; Risk; Societies; Subgroup; Time; Treatment Protocols; Tuberculosis; Viral; Work; antiretroviral therapy; arm; cost efficient; follow-up; meetings; mortality; participant enrollment; primary endpoint; randomized trial; response; symposium; trait; treatment group; treatment guidelines; treatment trial; trial design; virus genetics

Project Summary The Strategic Timing of Antiretroviral Treatment (START) is an international randomized trial designed to determine whether initiation of ART at CD4+ counts > 500 cells/mm3 (immediate or early ART) is superior in terms of morbidity and mortality to deferral of ART until the CD4+ declines to 350 cells/mm3 (deferred ART). On May 15, 2015 after an average of 3 years of follow-up, the independent Data and Safety Monitoring Board (DSMB) for START determined that the study primary question had been answered. Over an average follow-up of 3 years, immediate use of ART provided significant benefit over deferred ART for the primary endpoint (a composite of AIDS and non-AIDS events) of START (rates were 0.60 and 1.38 per 100 person years for the immediate and deferred ART groups. The DSMB recommended that results be immediately disseminated, that participants in the deferred ART group be offered ART, and recognizing the relatively short follow-up, that follow-up continue. With this proposal, investigators in the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) will continue follow-up of the 4,684 HIV-positive participants enrolled in START through December 2021, and carry out final data analyses aimed at determining whether the risk of major morbidity and mortality associated with delayed initiation is eliminated once ART is initiated and HIV RNA levels are suppressed or whether it persists. No prior randomized trial has addressed this question. Multiple papers will summarize the long-term follow-up findings and results will also be presented at scientific conferences.

项目概要 抗逆转录病毒治疗的战略时机（START）是一项国际随机试验 旨在确定是否在 CD4+ 计数 > 500 个细胞/mm3 时开始 ART（立即 或早期 ART）在发病率和死亡率方面优于推迟 ART 直至 CD4+ 下降至 350 个细胞/mm3（延迟 ART）。经过平均3年的时间后，2015年5月15日 后续，START的独立数据和安全监控委员会（DSMB）确定 研究的主要问题已经得到解答。平均随访 3 年， 就主要终点而言，立即使用 ART 比延迟 ART 具有显着优势 START（艾滋病毒和非艾滋病事件的综合）（比率为每 100 人 0.60 和 1.38） 立即和延期 ART 组的人年。 DSMB 建议 结果立即传播，为延迟 ART 组的参与者提供机会 ART，并认识到后续行动相对较短，后续行动仍在继续。有了这个提议， 全球艾滋病毒试验战略倡议国际网络的研究人员 (INSIGHT) 将继续跟踪 START 中登记的 4,684 名艾滋病毒阳性参与者 到 2021 年 12 月，并进行最终数据分析，以确定是否 一旦接受抗逆转录病毒治疗，与延迟开始相关的主要发病率和死亡率的风险就会被消除 是否启动且 HIV RNA 水平受到抑制或是否持续存在。之前没有随机试验 已经解答了这个问题。多篇论文将总结长期随访结果 结果还将在科学会议上公布。

项目成果

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.

• DOI: 10.1056/evidoa2200302
• 发表时间: 2023-03
• 期刊: NEJM evidence

Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.

• DOI: 10.1111/hiv.13038
• 发表时间: 2021-05
• 期刊: HIV medicine
• 影响因子: 3
• 作者: Baxter JD;Dunn D;Tostevin A;Marvig RL;Bennedbaek M;Cozzi-Lepri A;Sharma S;Kozal MJ;Gompels M;Pinto AN;Lundgren J;INSIGHT START Study Group
• 通讯作者: INSIGHT START Study Group

Genome-wide association study of high-sensitivity C-reactive protein, D-dimer, and interleukin-6 levels in multiethnic HIV+ cohorts.

• DOI: 10.1097/qad.0000000000002738
• 发表时间: 2021-02-02
• 期刊: AIDS (London, England)
• 作者: Sherman BT;Hu X;Singh K;Haine L;Rupert AW;Neaton JD;Lundgren JD;Imamichi T;Chang W;Lane HC;ESPRIT, SMART and START Study Groups
• 通讯作者: ESPRIT, SMART and START Study Groups

Phylogenetic analysis of HIV-1 shows frequent cross-country transmission and local population expansions.

• DOI: 10.1093/ve/veab055
• 发表时间: 2021
• 期刊: Virus evolution
• 影响因子: 5.3
• 作者: Bennedbæk M;Zhukova A;Tang ME;Bennet J;Munderi P;Ruxrungtham K;Gisslen M;Worobey M;Lundgren JD;Marvig RL
• 通讯作者: Marvig RL

The rate of bone loss slows after 1-2 years of initial antiretroviral therapy: final results of the Strategic Timing of Antiretroviral Therapy (START) bone mineral density substudy.

• DOI: 10.1111/hiv.12796
• 发表时间: 2020-01
• 期刊: HIV medicine
• 影响因子: 3
• 作者: Carr A;Grund B;Schwartz AV;Avihingsanon A;Badal-Faesen S;Bernadino JI;Estrada V;La Rosa A;Mallon P;Pujari S;White D;Wyman Engen N;Ensrud K;Hoy JF;International Network for Strategic Initiatives in Global HIV Trials START bone mineral density substudy group
• 通讯作者: International Network for Strategic Initiatives in Global HIV Trials START bone mineral density substudy group