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Title:	Different Plasma Markers of Inflammation Are Influenced by Immune Recovery and cART Composition or Intensification in Treated HIV Infected Individuals
Author:	Massanella, Marta; Ouchi, Dan; Marfil, Silvia; Llibre, Josep María; Puertas, Maria C.; Buzón, María J.; Richman, Douglas D.; Orna, Elisa; Stevenson, Mario; Gatell, José M.; Domingo, Pere (Domingo Pedrol); Negredo, Eugenia; Martínez Picado, Francisco Javier; Clotet i Sala, Bonaventura; Blanco, Julià
Notes:	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.
Subject(s):	-Marcadors bioquímics -Infeccions per VIH -Inflamació -Antiretrovirals -Biochemical markers -HIV infections -Inflammation -Antiretroviral agents
Rights:	cc-by (c) Massanella, Marta et al., 2014 http://creativecommons.org/licenses/by/3.0/es
Document type:	Article Article - Published version
Published by:	Public Library of Science (PLoS)
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