Petrara Maria Raffaella, Cattelan Anna Maria, Sasset Lolita, Freguja Riccardo, Carmona Francesco, Sanavia Silvia, Zanchetta Marisa, Del Bianco Paola, De Rossi Anita
Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, AIDS Reference Centre, University of Padova, Padova, Italy.
Division of Infectious and Tropical Diseases, Azienda Ospedaliera and University of Padova, Padova, Italy.
PLoS One. 2017 Sep 19;12(9):e0185128. doi: 10.1371/journal.pone.0185128. eCollection 2017.
Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear.
This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study. Markers of HIV-1 reservoir (HIV-1 DNA and intracellular HIV-1 RNA) were quantified by real-time PCR. Markers of T-(CD3+CD8+CD38+) and B-(CD19+CD80/86+ and CD19+CD10-CD21lowCD27+) cell activation were evaluated by flow cytometry. Plasma levels of microbial translocation markers were quantified by real-time PCR (16S ribosomal DNA and mitochondrial [mt]DNA) or by ELISA (LPS and sCD14). EBV was typed and quantified by multiplex real-time PCR.
At baseline, no differences were found between mART and cART groups. Three (10%) mART-treated patients had a virological failure vs none in the cART group. Levels of HIV-1 DNA, intracellular HIV-1 RNA and EBV-DNA remained stable in the mART group, while decreased significantly in the cART group. Percentages of T- and B-activated cells significantly increased in the mART-treated patients, while remained at low levels in the cART-treated ones (p = 0.014 and p<0.001, respectively). Notably, levels of mtDNA remained stable in the cART group, but significantly rose in the mART one (p<0.001).
Long-term mART is associated with higher levels of T- and B-cell activation and, conversely to cART, does not reduce the size of HIV-1 reservoir and EBV co-infection.
虽然单一疗法（mART）在维持HIV-1感染患者病毒抑制和CD4细胞计数方面的有效性已得到广泛研究，但其对HIV-1储存库、免疫激活、微生物易位以及与EB病毒（EBV）合并感染的影响尚不清楚。
这项回顾性研究纳入了32例转换为mART的患者；在基线、开始mART治疗后的48周和96周对患者进行研究。同时纳入了32例在同一时期继续接受联合抗逆转录病毒治疗（cART）的患者。通过实时PCR对HIV-1储存库标志物（HIV-1 DNA和细胞内HIV-1 RNA）进行定量。通过流式细胞术评估T细胞（CD3+CD8+CD38+）和B细胞（CD19+CD80/86+以及CD19+CD10-CD21lowCD27+）激活标志物。通过实时PCR（16S核糖体DNA和线粒体[mt]DNA）或ELISA（脂多糖和可溶性CD14）对血浆中微生物易位标志物水平进行定量。通过多重实时PCR对EBV进行分型和定量。
在基线时，mART组和cART组之间未发现差异。3例（10%）接受mART治疗的患者出现病毒学失败，而cART组无此情况。mART组中HIV-1 DNA、细胞内HIV-1 RNA和EBV-DNA水平保持稳定，而cART组中则显著下降。接受mART治疗的患者中T细胞和B细胞激活百分比显著增加，而接受cART治疗的患者中则维持在低水平（分别为p = 0.014和p<0.001）。值得注意的是，cART组中mtDNA水平保持稳定，但mART组中显著升高（p<0.001）。
长期mART与更高水平的T细胞和B细胞激活相关，与cART相反，它不会减小HIV-1储存库的大小和EBV合并感染率。
