Randomized clinical trial to evaluate the longitudinal HIV-1 reservoir and inflammation in treatment-naïve people starting dolutegravir/lamivudine vs. dolutegravir plus tenofovir alafenamide/emtricitabine.

IF 8.5 1区医学 Q1 INFECTIOUS DISEASES

Clinical Microbiology and Infection Pub Date : 2025-10-03 DOI:10.1016/j.cmi.2025.09.014

Abraham Saborido-Alconchel, Ana Serna-Gallego, María Trujillo-Rodriguez, Esperanza Muñoz-Muela, Ana I Alvarez-Ríos, Cesar Sotomayor, Marta Herrero, Luis E Lopez-Cortes, Nuria Espinosa, Miguel Raffo-Marquez, Alberto Romero-Palacios, Gabriel Mariscal-Vázquez, Antonio Rivero, Cristina Roca-Oporto, Alicia Gutierrez-Valencia, Luis F López-Cortes

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引用次数: 0

Abstract

Objective: There is limited evidence on whether dolutegravir/lamivudine (DTG/3TC) reduces the viral reservoir, immune activation, and inflammation as a three-drug regimen. This study aims to clarify possible differences in these outcomes in PHIV starting DTG plus tenofovir alafenamide/emtricitabine (DTG+TAF/F) versus DTG/3TC.

Methods: A phase IV, controlled, open-label, multicenter clinical trial in which treatment-naïve PHIV were randomized to DTG+TAF/F or DTG/3TC. The primary endpoint was changes in CD4⁺ T-cells associated HIV-1-DNA and -RNA after 12 and 24 months (Intact Proviral DNA and Intact Viral RNA Assays). Secondary endpoints included immune recovery and changes in T cell phenotypes and plasma inflammatory markers.

Statistics: χ², Mann-Whitney U test, and general linear model for repeated measures.

Results: Sixty-six participants were randomized, of whom 30 (DTG/3TC) and 29 (DTG +TAF/F) completed follow-up. Overall, the median baseline CD4⁺/μL count was 401 (293-540), the CD4⁺/CD8⁺ ratio 0.47 (0.34-0.76), and the viral load 57,250 copies/mL (16,189-180,500) Results are reported as medians (interquartile ranges) in the DTG+TAF/F and DTG/3TC groups at baseline and month 24, respectively. Intact HIV-1-DNA: 1,210 (412-3,508) copies/10⁶ CD4⁺ and 1,230 (335-2,502), which decreased to 65 (24-236) and 71 (32-110) (F= 0.253; p= 0.691). Total defective HIV-1-DNA: 831 copies/10⁶ CD4⁺ (315-1636) and 726 (273-1770), decreasing to 143 copies/10⁶ CD4⁺ (82-368) and 266 (67-353) (F= 1.840, p= 0.201). Likewise, no significant differences were observed between the groups in immune recovery, decrease in activation, proliferation, and exhaustion markers of T-cells, as well as in the reduction of plasma levels of IL-1β, IL-6, TNF-α, IFN-γ, sCD14, and sCD163.

Conclusions: These data suggest that starting treatment with DTG+TAF/F does not confer benefits over DTG/3TC.

查看原文本刊更多论文

随机临床试验评估纵向HIV-1储存库和炎症treatment-naïve人开始多替格拉韦/拉米夫定与多替格拉韦加替诺福韦阿拉那胺/恩曲他滨。

目的：关于多替格拉韦/拉米夫定（DTG/3TC）作为三药方案是否能降低病毒库、免疫激活和炎症的证据有限。本研究旨在阐明DTG+替诺福韦阿拉胺/恩曲他滨（DTG+TAF/F）与DTG/3TC在这些结果上可能存在的差异。方法：在一项IV期、对照、开放标签、多中心临床试验中，treatment-naïve PHIV随机分为DTG+TAF/F或DTG/3TC。主要终点是12个月和24个月后CD4+ t细胞相关HIV-1-DNA和-RNA的变化（完整的前病毒DNA和完整的病毒RNA测定）。次要终点包括免疫恢复、T细胞表型和血浆炎症标志物的变化。统计方法：χ2， Mann-Whitney U检验，重复测量采用一般线性模型。结果：随机选取66例受试者，其中30例（DTG/3TC）和29例（DTG +TAF/F）完成随访。总体而言，基线CD4+/μL计数中位数为401 (293-540)，CD4+/CD8+比值为0.47(0.34-0.76)，病毒载量为57,250拷贝/mL（16,189-180,500）。结果分别为DTG+TAF/F组和DTG/3TC组在基线和第24个月的中位数（四分位数范围）。完整的HIV-1-DNA: 1,210（412-3,508）拷贝/106 CD4+和1,230(335-2,502)，减少到65（24-236）和71 (32-110)（F= 0.253; p= 0.691）。总缺陷HIV-1-DNA: 831拷贝/106 CD4+(315-1636)和726拷贝/106 CD4+(273-1770)，减少到143拷贝/106 CD4+(82-368)和266拷贝/106 CD4+ (67-353) （F= 1.840, p= 0.201）。同样，两组之间在免疫恢复、t细胞活化、增殖和衰竭标志物的减少以及血浆IL-1β、IL-6、TNF-α、IFN-γ、sCD14和sCD163水平的降低方面也没有显著差异。结论：这些数据表明，DTG+TAF/F开始治疗并不比DTG/3TC更好。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Microbiology and Infection 医学-传染病学

CiteScore

25.30

自引率

2.10%

发文量

441

审稿时长

2-4 weeks

期刊介绍： Clinical Microbiology and Infection (CMI) is a monthly journal published by the European Society of Clinical Microbiology and Infectious Diseases. It focuses on peer-reviewed papers covering basic and applied research in microbiology, infectious diseases, virology, parasitology, immunology, and epidemiology as they relate to therapy and diagnostics.