 |
|
|
| |
Differential Effects of Maraviroc (MVC) and Efavirenz (EFV) on Markers of Immune Activation (IA) and Inflammation and Their Association with CD4 Cell Rises: A Sub-analysis of the MERIT
|
| |
| |
Reported by Jules Levin
ICAAC Sept 15 2009 San Francisco
N Funderburg1, M Kalinowska1, J Eason1, J Goodrich2, J Heera2, H Mayer3, N Rajicic3, H Valdez3, M Lederman1
1 Case Western Reserve University, Cleveland, OH, USA; 2 Pfizer Global Research and Development, New London, CT, USA; 3 Pfizer Inc, New York, NY, USA
For further information, please contact: Hernan Valdez, MD, Pfizer, Inc, New York, NY, 212-733-8058, hernan.valdez@pfizer.com
Compared with EFV-treated patients, MVC-treated patients had earlier modest decreases in several markers of immune activation and inflammation
This immunologic effect is in addition to the indirect antiviral mediated effect observed with both MVC and EFV
Decreases in CD4+ and CD8+ T cell activation correlated with increases from baseline in circulating CD4+ cells
Immune activation is a predictor and likely driver of HIV disease progression; decreasing immune activation by MVC may decrease CD4+ T cell turnover, and increase their numbers
Alternatively, CCR5 inhibition may prevent migration of T cells to peripheral tissues, thereby increasing cell numbers in circulation
BACKGROUND & OBJECTIVES
Untreated HIV-infection is associated with chronic immune activation (IA) and evidence of inflammation
Decreases in immune activation and inflammation during HAART have been associated with decreased expression of adhesion molecules and a redistribution of CD4+ cells from lymphoid tissues to blood1
- This redistribution may account for the rise in peripheral blood CD4+ cells that occurs early after HAART initiation
MVC treatment has been associated with larger increases in CD4+ cell counts than is attributable to its antiviral activity2-5
- Differences in CD4+ rises between MVC and control occur early in therapy2,4
It is unknown whether these CD4+ cell rises are related to MVC's potential effect on markers of immune activation or inflammation
We analyzed a subset of patients from the MERIT study to explore whether MVC for HIV-infected treatment-naive patients has different effects than EFV on clinically relevant markers of immune activation and inflammation
Secondary objectives included:
- Explaining differences in clinical or laboratory outcomes in the MERIT study
- Exploring whether MVC has early immunologic effects beyond those expected after antiviral activity
- Identifying potential clinical markers to be studied prospectively
|
| |
|
|
|
|
|
