BenMarzouk-Hidalgo Omar J, Torres-Cornejo Almudena, Gutiérrez-Valencia Alicia, Ruiz-Valderas Rosa, Viciana Pompeyo, López-Cortés Luis F
From the Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva. Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avenida Manuel Siurot, Sevilla, Spain.
Medicine (Baltimore). 2015 May;94(17):e781. doi: 10.1097/MD.0000000000000781.
The purpose of this article is to evaluate the evolution of microbial translocation (MT) and its role in CD4 and CD8 T cells immune activation (IA) in HIV-1-infected patients on ritonavir-boosted darunavir monotherapy (mtDRV/rtv).Prospective study of consecutive HIV-1-infected patients switched to mtDRV/rtv as a simplification regimen. Subjects were classified according to the virological behavior during a 24-month follow-up as continuous undetectable viral load, blips, intermittent viremia, and virological failure (VF). MT was evaluated by plasma LPS and 16S genomic rDNA (16S rDNA) levels, whereas IA was assessed by the coexpression of HLA-DR and CD38 in CD4 and CD8 T cells, and plasma sCD14 levels.Seventy-one patients were included in this substudy of the MonDar cohort (ClinicalTrials.gov: NCT01505722). At baseline, CD4 (ρ = -0.352, P = 0.01) and CD8 T-cell activation (ρ = -0.468, P < 0.001) were correlated with time with viral suppression, but not with MT markers. A significant decrease in plasma LPS levels was found only in patients without VF (baseline, 77.8 vs month 24, 60.4 pg/mL; P < 0.001]. Both plasma 16S rDNA and sCD14 levels were unchanged irrespective of the viral behavior. The only variable independently associated with a decrease in CD4 and CD8 T cells activation was an undetectable HIV-1 viremia (β = 4.78, P < 0.001 and β = 2.93, P = 0.005, respectively).MT does not have a pivotal role in T-cell activation, at least in patients with long-term viral suppression. The viremic episodes and VF are the main factors related to CD4 and CD8 T-cells IA, even during mtDRV/rtv.
本文旨在评估微生物易位(MT)的演变及其在接受利托那韦增强达芦那韦单药治疗(mtDRV/rtv)的HIV-1感染患者的CD4和CD8 T细胞免疫激活(IA)中的作用。对连续的HIV-1感染患者转为mtDRV/rtv作为简化治疗方案进行前瞻性研究。根据24个月随访期间的病毒学行为,将受试者分为病毒载量持续不可检测、病毒载量波动、间歇性病毒血症和病毒学失败(VF)。通过血浆脂多糖(LPS)和16S基因组rDNA(16S rDNA)水平评估MT,而通过CD4和CD8 T细胞中HLA-DR和CD38的共表达以及血浆可溶性CD14(sCD14)水平评估IA。本研究纳入了MonDar队列(ClinicalTrials.gov:NCT01505722)的71例患者。基线时,CD4(ρ = -0.352,P = 0.01)和CD8 T细胞激活(ρ = -0.468,P < 0.001)与病毒抑制时间相关,但与MT标志物无关。仅在无VF的患者中发现血浆LPS水平显著降低(基线时为77.8 pg/mL,第24个月时为60.4 pg/mL;P < 0.001)。无论病毒行为如何,血浆16S rDNA和sCD14水平均无变化。与CD4和CD8 T细胞激活降低独立相关的唯一变量是HIV-1病毒血症不可检测(β = 4.78,P < 0.001和β = 2.93,P = 0.005)。MT在T细胞激活中没有关键作用,至少在长期病毒抑制的患者中如此。病毒血症发作和VF是与CD4和CD8 T细胞IA相关的主要因素,即使在mtDRV/rtv治疗期间也是如此。