时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
The DEBATE study is a randomized clinical trial (RCT) designed to evaluate and compare immunological outcomes in people with HIV (PWH) who maintain viral suppression.；DTG/3TC is the first dual ART to be included in all international guidelines as a recommended regimen for PWH, whether they are ART-naïve or experienced.；In the DEBATE trial, over 12 months, no significant differences were observed between the two groups in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, or plasma IL-6 levels, indicating overall immunological stability following regimen simplification.
方法
Participants included in the present study were selected from the DEBATE trial cohort.；Thus, only participants for whom a baseline sample (T0) was still available and suitable for the present experimental analyses were included ().；Paired samples collected at baseline (T0) and at the 36-month follow-up (T3) were analyzed.；The study (EudraCT number 2018-003458-26; ClinicalTrials.gov identifier ) was approved by the local Ethics Committee (EC) (authorization number AOU 0010923/19, April 4, 2019) and by the Italian Medicines Agency (AIFA) (authorization number AIFA/SC/P/33830, March 25, 2019).
核心结论
Monocyte phenotype differed significantly between T0 and T3 (R2 = 0.175, p = 0.0065, permutations restricted within patient), and PC1 shifted in the same direction in 10 of 11 patients (p = 0.011), indicating a consistent change at the individual level.；The two regimens were indistinguishable at baseline (p = 0.78) and differed at T3 (R2 = 0.199, p = 0.023), but the magnitude of the within-patient change did not differ between them (p = 0.43); given the small group sizes, this comparison is considered exploratory.；In particular, PWH treated with B/F/TAF show a significant decrease in two of the intermediate clusters (C2 and C3) characterized by the expression of high levels of MerTK as well as CD209, p16 and CD38. ‖ 结论：In conclusion, these findings challenge the assumption that modern two- or three-drug regimens with a high barrier to resistance confer immunological equivalence beyond virological suppression, and they underscore the need to study adjunctive immunomodulatory strategies, such as anti-inflammatory agents, checkpoint inhibitors, or targeted senolytic approaches, to complement ART in addressing the residual immune dysfunction that persists despite optimal virological control.
局限
Whether increased pSTAT3 in monocytes directly or indirectly influences HIV reservoir maintenance remains to be determined and warrants further investigation.；Switching from a 3DR to either another 3DR or a 2DR does not appear to normalize innate immune activation, underscoring the need for adjunctive strategies to mitigate residual inflammation in PWH.；Persistent monocyte alterations despite effective viral suppression may represent a pivotal biological link to residual non-AIDS morbidity in long-term treated HIV infection.
对本项目的价值
★★☆☆☆ 炎症衰老是几乎所有慢性老年病的公共通路，也是最有希望做「抗炎但保留免疫」解耦的靶点。
全文来源
PMC JATS 全文（正文 25,379 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Persistent monocyte activation and remodeling in people with HIV after 36 months of switching from a 3-drug regimen to B/F/TAF or DTG/3TC: a sub-study of the DEBATE trial.
- 期刊与标识：Front Immunol · PMID 42953116 · DOI 10.3389/fimmu.2026.1957183
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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