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

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.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 9 Issue 12 Pg. e114142 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25462535 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biomarkers
• HIV Integrase Inhibitors
• Raltegravir Potassium

Topics

• Adult
• Biomarkers (blood)
• Female
• HIV Infections (blood, drug therapy, immunology)
• HIV Integrase Inhibitors (administration & dosage, therapeutic use)
• Humans
• Inflammation (blood)
• Male
• Middle Aged
• Prospective Studies
• Raltegravir Potassium (administration & dosage, therapeutic use)