Different plasma markers of inflammation are influenced by immune recovery and cART composition or intensification in treated HIV infected individuals

Marta Massanella, Dan Ouchi, Silvia Marfil, Josep M. Llibre, Maria C. Puertas, María J. Buzón, Douglas D. Richman, Elisa Orna, Mario Stevenson, Josep M. Gatell, Pere Domingo, Eugènia Negredo, Javier Martinez-Picado, Bonaventura Clotet, Julià Blanco

Research output: Contribution to journalArticle

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Abstract

Background: HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies. Methods: Longitudinal plasma samples (0-48 weeks) from the IntegRal (n=67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts,350 cells/μl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis. Results: At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P=0.040). Conclusions: The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers.

Original languageEnglish
Article numbere114142
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 2 2014

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T-cells
inflammation
HIV
Inflammation
Plasmas
Recovery
therapeutics
Protease Inhibitors
CD4 Lymphocyte Count
T-lymphocytes
proteinase inhibitors
Chemical analysis
T-Lymphocytes
virus replication
Coinfection
mixed infection
Chemical activation
Association reactions
Therapeutics
Coagulation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Different plasma markers of inflammation are influenced by immune recovery and cART composition or intensification in treated HIV infected individuals. / Massanella, Marta; Ouchi, Dan; Marfil, Silvia; Llibre, Josep M.; Puertas, Maria C.; Buzón, María J.; Richman, Douglas D.; Orna, Elisa; Stevenson, Mario; Gatell, Josep M.; Domingo, Pere; Negredo, Eugènia; Martinez-Picado, Javier; Clotet, Bonaventura; Blanco, Julià.

In: PLoS One, Vol. 9, No. 12, e114142, 02.12.2014.

Research output: Contribution to journalArticle

Massanella, M, Ouchi, D, Marfil, S, Llibre, JM, Puertas, MC, Buzón, MJ, Richman, DD, Orna, E, Stevenson, M, Gatell, JM, Domingo, P, Negredo, E, Martinez-Picado, J, Clotet, B & Blanco, J 2014, 'Different plasma markers of inflammation are influenced by immune recovery and cART composition or intensification in treated HIV infected individuals', PLoS One, vol. 9, no. 12, e114142. https://doi.org/10.1371/journal.pone.0114142
Massanella, Marta ; Ouchi, Dan ; Marfil, Silvia ; Llibre, Josep M. ; Puertas, Maria C. ; Buzón, María J. ; Richman, Douglas D. ; Orna, Elisa ; Stevenson, Mario ; Gatell, Josep M. ; Domingo, Pere ; Negredo, Eugènia ; Martinez-Picado, Javier ; Clotet, Bonaventura ; Blanco, Julià. / Different plasma markers of inflammation are influenced by immune recovery and cART composition or intensification in treated HIV infected individuals. In: PLoS One. 2014 ; Vol. 9, No. 12.
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abstract = "Background: HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies. Methods: Longitudinal plasma samples (0-48 weeks) from the IntegRal (n=67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts,350 cells/μl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis. Results: At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P=0.040). Conclusions: The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers.",
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AU - Massanella, Marta

AU - Ouchi, Dan

AU - Marfil, Silvia

AU - Llibre, Josep M.

AU - Puertas, Maria C.

AU - Buzón, María J.

AU - Richman, Douglas D.

AU - Orna, Elisa

AU - Stevenson, Mario

AU - Gatell, Josep M.

AU - Domingo, Pere

AU - Negredo, Eugènia

AU - Martinez-Picado, Javier

AU - Clotet, Bonaventura

AU - Blanco, Julià

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N2 - Background: HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies. Methods: Longitudinal plasma samples (0-48 weeks) from the IntegRal (n=67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts,350 cells/μl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis. Results: At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P=0.040). Conclusions: The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers.

AB - Background: HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies. Methods: Longitudinal plasma samples (0-48 weeks) from the IntegRal (n=67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts,350 cells/μl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis. Results: At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P=0.040). Conclusions: The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers.

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