Different Plasma Markers of Inflammation Are Influenced by Immune Recovery and cART Composition or Intensification in Treated HIV Infected Individuals

作者：Massanella Marta; Ouchi Dan; Marfil Silvia; Llibre Josep M; Puertas Maria C; Buzon Maria J; Richman Douglas D; Orna Elisa; Stevenson Mario; Gatell Josep M; Domingo Pere; Negredo Eugenia; Martinez Picado Javier; Clotet Bonaventura; Blanco Julia^*

来源：PLos One, 2014, 9(12): e114142.

DOI：10.1371/journal.pone.0114142

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. %26lt;br%26gt;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%26lt;350 cells/mu l, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis. %26lt;br%26gt;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). %26lt;br%26gt;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.

• 出版日期2014-12-2