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

14 Scopus citations

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 (US)
Article numbere114142
JournalPloS one
Volume9
Issue number12
DOIs
StatePublished - Dec 2 2014

ASJC Scopus subject areas

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

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    Massanella, M., Ouchi, D., Marfil, S., Llibre, J. M., Puertas, M. C., Buzón, M. J., Richman, D. D., Orna, E., Stevenson, M., Gatell, J. M., 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, 9(12), [e114142]. https://doi.org/10.1371/journal.pone.0114142