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Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus.

Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus.
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Petrara MR, Cattelan AM, Sasset L, Freguja R, Carmona F, Sanavia S, Zanchetta M, Del Bianco P, De Rossi A,


Petrara MR, Cattelan AM, Sasset L, Freguja R, Carmona F, Sanavia S, Zanchetta M, Del Bianco P, De Rossi A, (click to view)

Petrara MR, Cattelan AM, Sasset L, Freguja R, Carmona F, Sanavia S, Zanchetta M, Del Bianco P, De Rossi A,

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PloS one 2017 09 1912(9) e0185128 doi 10.1371/journal.pone.0185128

Abstract
OBJECTIVES
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.

METHODS
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.

RESULTS
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). CONCLUSIONS
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.

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