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PLoS One. 2014 Dec 2;9(12):e114142. doi: 10.1371/journal.pone.0114142. eCollection 2014.

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

Author information

1
AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain; VA San Diego Healthcare System and Departments of Pathology and Medicine, University of California San Diego (UCSD), San Diego, United States of America.
2
AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain.
3
"Lluita contra la SIDA" Foundation, University Hospital Germans Trias i Pujol, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain.
4
VA San Diego Healthcare System and Departments of Pathology and Medicine, University of California San Diego (UCSD), San Diego, United States of America.
5
Hematology Department, University Hospital Germans Trias i Pujol, Badalona, Spain.
6
University of Miami, Miami, United States of America.
7
Hospital Clínic-IDIBAPS, Barcelona, Spain.
8
Hospital de Sant Pau, Barcelona, Spain.
9
"Lluita contra la SIDA" Foundation, University Hospital Germans Trias i Pujol, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain; Universitat de Vic-UCC, Vic, Spain.
10
AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain; Universitat de Vic-UCC, Vic, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
11
AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain; "Lluita contra la SIDA" Foundation, University Hospital Germans Trias i Pujol, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain; Universitat de Vic-UCC, Vic, Spain.
12
AIDS Research Institute IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, UAB, Badalona, Spain; Universitat de Vic-UCC, Vic, Spain.

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.

PMID:
25462535
PMCID:
PMC4252101
DOI:
10.1371/journal.pone.0114142
[Indexed for MEDLINE]
Free PMC Article

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