Chair of Pathology and Immunology, University of Modena and Reggio Emilia School of Medicine, Modena, Italy.
Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London (UCL), London, United Kingdom.
Front Immunol. 2023 Oct 16;14:1279390. doi: 10.3389/fimmu.2023.1279390. eCollection 2023.
The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR).
An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders.
Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm-time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = -6.7 cells/mm; 95% CI; -16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12.
No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results.
https://clinicaltrials.gov, identifier NCT04054089.
本随机临床试验（RCT）旨在比较接受三药治疗方案（3DR）的病毒抑制的艾滋病毒感染者（PLWH）切换至二药治疗方案（2DR）后的免疫变化。
对接受 3DR 的 PLWH 进行了一项开放标签、前瞻性 RCT，这些患者转换为比替拉韦/恩曲他滨/替诺福韦艾拉酚胺（B/F/TAF）或多替拉韦/拉米夫定（DTG/3TC）。在基线和第 6 个月和第 12 个月采集血液。主要结局是随着时间点的推移，CD4+或 CD8+ T 细胞计数和 CD4/CD8 比值的变化。次要结局是免疫和炎症参数的变化。在控制潜在混杂因素后，分别针对每个标志物拟合具有随机截距和斜率的参数混合线性模型。
在两个治疗臂（各 33 名 PLWH）之间，CD4+或 CD8+ T 细胞、CD4/CD8 比值和 IL-6 轨迹没有差异。转换为 DTG/3TC 的 PLWH 具有更高水平的过渡性记忆和终末分化的 CD4+ T 细胞（手臂时间交互作用 p 值=0.02），而相应的 CD8+ T 细胞亚群则较低（p=0.09）。在 B/F/TAF 臂中，在 T6 时检测到非经典单核细胞水平显著降低（差异=-6.7 个细胞/mm；95%CI：-16，+2.6；手臂与时间之间的交互作用 p 值=0.03）。所有差异在 T12 时均减弱。
在 12 个月内，未发现研究臂之间绝对 CD4+和 CD8+ T 细胞计数、CD4/CD8 比值和 IL-6 轨迹存在差异。在 T6 时，接受 DTG/3TC 的 PLWH 具有更高水平的终末分化和耗竭的 CD4+和 CD8+ T 淋巴细胞以及非经典单核细胞。需要进一步的研究来更好地了解我们结果的临床影响。
https://clinicaltrials.gov，标识符 NCT04054089。
